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Antineoplastic agents a6

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  • Autologous clonal neoantigen t cells atl001 - A preparation of personalized tumor-derived T-lymphocytes composed of tumor infiltrating lymphocytes (TILs) that are reactive to clonal cancer neoantigens, with potential immunostimulating and antineoplastic activities. The TILs are removed from the suppressive tumor microenvironment (TME) and re-activated. Upon reintroduction into the patient, the clonal neoantigen T (cNeT) cells recognize and bind to tumor cells expressing the targeted neoantigen, resulting in a cytotoxic T-lymphocyte (CTL)-mediated immune response against the patient's tumor cells.
  • Autologous c-met/pd-l1-specific car t-cells - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) specific for human hepatocyte growth factor receptor (HGFR or c-Met) and the immunosuppressive ligand, programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with potential antineoplastic activities. Upon infusion, the autologous c-Met/PD-L1-specific CAR T-cells bind to and induce selective toxicity in c-Met- and PD-L1-expressing tumor cells. cMET, a receptor tyrosine kinase that is overexpressed or mutated in many tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis. PD-L1 is also overexpressed by many human cancer cell types and plays a key role in the downregulation of the immune system and tumor evasion from host immunity.
  • Autologous cmv-pp65-fllamp mrna loaded dendritic cell vaccine - A cancer cell vaccine consisting of autologous dendritic cells (DCs) loaded with mRNA encoding the human cytomegalovirus (CMV) matrix protein pp65 (65 kDa lower matrix phosphoprotein; UL83) as a fusion protein with the full-length lysosome-associated membrane protein (flLAMP), with potential immunostimulatory and antineoplastic activities. Upon vaccination, the autologous CMV-pp65-flLAMP mRNA loaded DC vaccine exposes the immune system to the CMV pp65 peptide, which may elicit a cytotoxic T-lymphocyte (CTL) response against CMV pp65-expressing tumor cells. The incorporation of flLAMP may route CMV pp-65 antigens into the lysosomal compartment, resulting in enhanced MHC class II antigen presentation, thereby promoting CD4-positive T-cell responses. The CMV pp65 protein is the primary component of the enveloped subviral particle of CMV and is expressed in certain tumor types.
  • Autologous cmv-pp65-shlamp-1 mrna loaded dendritic cell vaccine - A cancer cell vaccine consisting of autologous dendritic cells pulsed with mRNA encoding the human cytomegalovirus (CMV) matrix protein pp65 (65 kDa lower matrix phosphoprotein; UL83) as a fusion construct with a short peptide chimeric antigen from lysosome-associated membrane protein 1 (shLAMP-1), with potential antineoplastic and immunostimulatory activities. Upon vaccination, the autologous CMV-pp65-shLAMP-1 vaccine exposes the immune system to the CMV pp65 peptide, which may elicit a cytotoxic T-lymphocyte (CTL) response against CMV pp65-expressing tumor cells. The incorporation of shLAMP-1 may route CMV pp-65 antigens into the lysosomal compartment, resulting in enhanced MHC class II antigen presentation, thereby promoting CD4-positive T-cell responses. The CMV pp65 protein is the primary component of the enveloped sub-viral particle of CMV and is expressed in certain tumor types.
  • Autologous colon cancer cell vaccine - A personalized, proprietary cancer vaccine composed of sterile, irradiated, non-dividing, live colon cancer cells obtained from an individual after tumor resection, with potential immunoactivating and antineoplastic activities. Upon intradermal administration, the autologous colon cancer cell vaccine activates the immune system and elicits a cytotoxic T-lymphocytic (CTL) response against the residual colon cancer cells, which results in tumor cell death. This may prevent cancer recurrence. According to the vaccination schedule, the first two out of the four doses are co-administered with the immunoadjuvant bacillus Calmette-Guerin (BCG), which is an attenuated strain of Mycobacterium bovis that non-specifically enhances the immune response.
  • Autologous colorectal tumor antigen-pulsed dendritic cell vaccine - A dendritic cell (DC)-based cancer vaccine composed of autologous DCs pulsed with tumor cell lysates from a colorectal cancer patient containing tumor-associated antigens (TAAs), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous colorectal tumor antigen-pulsed DC vaccine exposes the immune system to colorectal tumor cell antigens, which may result in cytotoxic T-lymphocyte (CTL)-mediated immune responses against the colorectal cancer cells. This leads to cancer cell lysis. The tumor cell lysate contains a range of antigens that are essential for the neoplastic growth and survival of the cancer cells.
  • Autologous crispr-edited anti-cd19 car t cells xyf19 - A preparation of autologous T-lymphocytes transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD19, and electroporated with clustered regularly interspaced short palindromic repeats (CRISPR) guide RNA to disrupt expression of endogenous hematopoietic progenitor kinase 1 (HPK1), with potential immunostimulating and antineoplastic activities. Upon introduction into the patient, the autologous CRISPR-edited anti-CD19 CAR T-cells XYF19 recognize and bind to CD19-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of CD19-positive tumor cells. Disrupting the expression of HPK1 may enhance immune response and autoimmunity. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. HPK1 is a Ste20-like serine/threonine kinase that suppresses immune responses and autoimmunity.
  • Autologous ct7/mage-a3/wt1 mrna-electroporated langerhans-type dendritic cells - An autologous tumor cell vaccine containing CD34+ hematopoietic progenitor cell (HPC)-derived Langerhans-type dendritic cells (LCs) electroporated with mRNA encoding the full-length cancer-testis antigens, CT7 and melanoma-associated antigen 3 (MAGE-A3), and the self-differentiation tumor antigen, Wilms tumor 1 (WT1) with potential immunomodulating and antineoplastic activity. The autologous CT7/MAGE-A3/WT1 mRNA-electroporated Langerhans-type dendritic cells are prepared by drawing a blood sample containing the CD34+ HPCs from a cancer patient. The CD34+ HPCs are treated with a combination of cytokines which specifically support LC development, and the LC population is enriched and expanded ex vivo. The cultured LCs are allowed to mature for one day and then electroporated separately with CT7, MAGE-A3 or WT1 mRNA before final maturation. Upon intradermal administration into the patient, the mature LCs may activate cell-mediated immunity and induce both cytotoxic CD8+ T cells and CD4+ helper T cells against cancer cells expressing CT7, MAGE-A3 and WT1 tumor antigens. This may result in the immune-mediated inhibition of tumor cell proliferation, leading to tumor cell death. CT7 and MAGE-A3 are tumor-specific proteins overexpressed in a number of cancers but not in healthy tissues other than testis and placenta. WT1 is a transcription factor important in development and cancer pathogenesis, which is overexpressed in a variety of cancers, including multiple myeloma, leukemia, ovarian cancer, malignant mesothelioma, neural tumors and renal carcinoma.
  • Autologous ct-rcc-1 herv-e-tcr-transduced-hla-a11-restricted cd8+/cd34t+ t-cells - A preparation of autologous T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) sequence specific for CT-RCC-1, a tumor-associated antigen (TAA) and HLA-A11-restricted peptide encoded by human endogenous retrovirus (HERV) type E as well as a truncated CD34 chain (CD34t), with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo and re-introduction into the patient, the autologous CT-RCC-1 HERV-E-TCR-transduced-HLA-A11-restricted CD8+/CD34t+ T-cells bind to and induce selective toxicity in tumor cells expressing both the HLA-A11 allele and the CT-RCC-1 HERV-E antigen. The CD34t protein allows the transduced cells to be identified with an anti-CD34 antibody, and facilitates monitoring of the genetically modified T-cells following adoptive transfer. CT-RCC-1 HERV-E is a TAA found in a high percentage of clear cell renal cell carcinoma (ccRCC) cells.
  • Autologous cultured acute myeloid leukemia-specific cytotoxic t lymphocytes - A preparation of cytotoxic, autologous acute myelogenous leukemia (AML)-reactive T lymphocytes (CTL), with potential immunomodulating and antineoplastic activities. The autologous cultured AML-specific CTLs are prepared using a specific AML-CTL culture method. Autologous peripheral blood lymphocytes are taken from an AML patient and the autologous AML blasts are treated with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), both of which promote ex vivo differentiation of AML blasts into dendritic cells (DCs). In the same culture, T cells are treated and activated by low-dose interleukin 2 (IL-2), and expanded using anti-CD3. This results in cultured AML-reactive CTLs which are administered back into the patient after autologous hematopoietic stem cell transplant (AHSCT). The autologous cultured AML-specific CTLs may eradicate residual AML cells.
  • Autologous cytokine-induced killer cells - A proprietary formulation of autologous cytokine-induced killer (CIK) T-lymphocytes, with immunopotentiating and antineoplastic activities. These CIK cells are generated by ex vivo incubation of autologous peripheral blood lymphocytes with an undisclosed mixture of compounds to stimulate killer T-cell differentiation; this is followed by expansion of the cells. Upon reintroduction into the patient, the autologous CIK cells are able to target and kill tumor cells.
  • Autologous cytoplasmic activated pd-1 car t-cells - A preparation of autologous T-lymphocytes engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19), carrying cytoplasmic activated programmed cell death 1 (PD1; PDCD1; CD279; programmed death-1), with potential antineoplastic activity. Upon intravenous administration, autologous cytoplasmic activated PD-1 CAR T-cells target, bind to, and induce selective toxicity in CD19-expressing tumor cells. The cytoplasmic activated PD1, a negative immunoregulatory human cell surface receptor, normally binds to programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) on tumor cells, causing T-cell inactivation. By preventing PD1/PD-L1 signaling, T-cell exhaustion is abrogated, and T-cell activation is enhanced leading to an increased cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells. CD19 is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors.
  • Autologous cytotoxic t-lymphocytes exposed to dendritic cells loaded with 6b11 anti-idiotype minibody - A preparation of autologous cytotoxic T-lymphocytes (CTLs) that are exposed, ex vivo, to autologous dendritic cells (DCs) loaded with the anti-idiotype minibody 6B11, which mimics the epithelial ovarian tumor-associated antigen (TAA), OC166-9, with potential immunostimulatory and antineoplastic activities. Upon administration, the CTLs exposed to DCs loaded with 6B11 anti-idiotype minibody target and kill autologous ovarian cells expressing the TAA.
  • Autologous cytotoxic t-lymphocytes induced with muc1 gene-transfected dendritic cells - A preparation of autologous cytotoxic T-lymphocytes (CTL), specifically reactive to the tumor-associated antigen (TAA) mucin-1 (MUC1), with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMCs) are collected from the patient with MUC1-positive tumors and are exposed ex vivo to dendritic cells (DCs) transfected with a replication-deficient adenovirus encoding MUC1 to generate MUC1-specific CTLs, which are subsequently expanded in vitro. Upon re-infusion of autologous CTLs induced with MUC1 gene-transfected DCs to the patient, the CTLs target and lyse the MUC1-expressing tumor cells. This inhibits tumor cell proliferation. MUC1 is expressed by a variety of tumor cell types.
  • Autologous cytotoxic t-lymphocytes induced with muc1 peptide-pulsed dendritic cells - A preparation of autologous cytotoxic T-lymphocytes (CTL), specifically reactive to the tumor-associated antigen (TAA) mucin-1 (MUC1), with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMCs) are collected from the patient with MUC1-positive tumors and are exposed ex vivo to dendritic cells (DCs) that are pulsed with a MUC1 peptide to generate MUC1-specific CTLs, which are subsequently expanded in vitro. Upon re-infusion of autologous CTLs induced with MUC1 peptide-pulsed DCs to the patient, the CTLs target and lyse the MUC1-expressing tumor cells. This inhibits tumor cell proliferation. MUC1 is expressed by a variety of tumor cell types.
  • Autologous deep il-15 primed t-cells trq15-01 - A preparation of genetically modified, multi-antigen-directed autologous T-lymphocytes, that have particles, consisting of multiple chemically crosslinked human cytokine interleukin-15 (IL-15)/IL-15 receptor alpha (IL-15Ra)/Fc heterodimers, attached to their surface, with potential immunostimulating and antineoplastic activities. TRQ15-01 is made from monocyte-derived dendritic cells (moDCs) that are pulsed with peptides from multiple tumor-associated antigens (TAAs) to expand cytotoxic T-lymphocytes (CTLs) that are subsequently loaded with IL-15 particles. Upon administration of the autologous deep IL-15 primed T-cells, the IL-15/IL-15Ra fusion proteins are slowly released in vivo from the T-cells in a controlled manner and induce autocrine cytokine stimulation of the administered T-cells, thereby increasing T-cell division of the administered T-cells. The expanded T-cells target, bind to and kill tumor cells. This increases tumor cell growth inhibition by T-cells. IL-15 is a pro-survival, inflammatory cytokine and causes sustained T-cell expansion and enhanced anti-tumor activity. Compared to systemically delivered IL-15, IL-15 attached to the T-cells greatly increases target CD8 T-cell concentrations in the tumor, without significant systemic effects.
  • Autologous dendritic cell vaccine act2001 - A cell-based cancer vaccine composed of autologous, immature dendritic cells (DCs), with potential immunostimulating and antineoplastic activities. Upon leukapheresis, immature DCs are isolated and re-administered intra-tumorally. The immature DCs internalize and process the tumor-associated antigens (TAAs), migrate to the lymphatic system, and then expose the immune system to the TAAs. This induces a specific cytotoxic T-lymphocyte (CTL) response against the cancer cells leading to tumor cell lysis.
  • Autologous dendritic cell/myeloma fusion vaccine - A therapeutic cancer vaccine consisting of autologous dendritic cells (DCs) fused with patient-derived plasma cell (multiple) myeloma cells with potential immunostimulatory and antineoplastic activities. Upon administration, autologous DC/multiple myeloma fusions stimulate both helper and cytotoxic T-lymphocyte (CTL) responses through the presentation of internalized and newly synthesized tumor associated antigens (TAAs). This may promote cellular and humoral antitumor immune responses in patients with plasma cell myeloma.
  • Autologous dendritic cell-adenovirus ccl21 vaccine - A cancer vaccine comprised of autologous dendritic cells (DCs) that have been transduced ex vivo with an adenoviral vector containing the CCL21 gene with potential immunostimulatory and antineoplastic activities. Upon intratumoral administration, autologous dendritic cell-adenovirus CCL21 vaccine expresses the chemokine CCL21, which may induce an antitumoral cytotoxic immune response in the tumor microenvironment. CCL21 [chemokine (C-C motif) ligand 21] has been shown to attract antigen presenting cells (APCs), like leukocytes and DCs, and natural killer (NK) cells and their T-cell effectors to induce a cytotoxic immune response.
  • Autologous dendritic cell-adenovirus p53 vaccine - An autologous vaccine composed of dendritic cells (DC) that have been transduced with a p53 tumor suppressor gene-modified virus. When the autologous dendritic cell-adenovirus p53 vaccine is administered, the host cytotoxic T lymphocytes (CTL) are directed against p53-positive tumor cells, which may result in tumor cell death and decreased tumor growth.
  • Autologous dendritic cell-allogeneic melanoma tumor cell lysate vaccine - A cell-based vaccine composed of autologous dendritic cells (DCs) pulsed with lysates from heat-treated allogeneic melanoma tumor cells. Upon administration, this vaccine may stimulate anti-tumoral cytotoxic T-cell and antibody responses to melanoma cells bearing shared melanoma antigens such as MelanA/MART-1, gp100, MAGE3, resulting in tumor cell lysis.
  • Autologous dendritic cell-autologous tumor mrna-human cd40l vaccine - A cancer vaccine consisting of autologous dendritic cells transfected with autologous tumor mRNA and the human CD40 ligand (CD40L) gene with immunostimulatory and antitumor activities. Vaccination with autologous dendritic cell-autologous tumor mRNA-human CD40L vaccine may elicit a cytotoxic T cell response against tumor cells from which the autologous tumor mRNA was derived. When expressed by dendritic cells, tumor antigens and the co-stimulatory molecule CD40L, which binds to CD40 receptors on antigen presenting cells (APC), facilitate both humoral and cellular immune responses against tumor cells.
  • Autologous dendritic cells pulsed with mart-1 (26-35) peptide - A cell-based vaccine consisting of autologous HLA-A2*0201-restricted dendritic cells (DC), which were derived from patient-harvested adherent peripheral blood monocytes cultured in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), that were pulsed with a peptide fragment comprised of amino acid residues 26 through 35 of melanoma antigen recognized by T-cells 1 (MART-1 (26-35)), with potential immunostimulatory and antineoplastic activities. Upon intradermal vaccination, autologous DC pulsed with MART-1 (26-35) peptide may stimulate the host immune system to mount a cytotoxic T-lymphocyte immune response against tumor cells expressing MART-1. MART-1, a protein involved in melanosome biogenesis, is overexpressed by melanoma cells. The MART-1 (26-35) peptide is highly immunogenic for the HLA-A2*0201 haplotype.
  • Autologous dendritic cells transduced with wild-type p53 adenovirus vaccine - A cancer vaccine consisting of autologous dendritic cells (DCs) transduced with a recombinant replication-defective adenoviral (Ad) vector encoding the full-length wild-type (wt) cancer tumor antigen p53 protein (TP53; p53), with potential immunomodulating activity. Intradermal vaccination with the autologous DCs transduced with wt p53 Ad vaccine may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells overexpressing wt and mutant forms of p53, resulting in tumor cell lysis. p53, a tumor suppressor gene, is overexpressed and/or mutated in many tumor cells, resulting in the loss of apoptosis regulation and abnormal cell proliferation.
  • Autologous dendritic cell-tumor fusion vaccine - A therapeutic cancer vaccine consisting of autologous dendritic cells (DCs) fused with autologous tumor cells with potential immunostimulatory and antineoplastic activities. Autologous dendritic cell-tumor fusion vaccine is generated in vitro by mixing DCs and irradiated tumor cells harvested from individual patients and treating them with polyethylene glycol (PEG) to produce DC-tumor cell fusion hybrid cells. Upon administration, autologous dendritic cell-tumor fusion vaccine may elicit antitumor humoral and cellular immune responses.
  • Autologous dinitrophenyl-modified ovarian cancer vaccine - A cancer vaccine consisting of autologous ovarian cancer cell peptide antigens conjugated to the hapten 2,4-dinitrophenol (DNP) with potential immunostimulating and antineoplastic activities. Administration of autologous dinitrophenyl-modified ovarian cancer vaccine may induce a cytotoxic T-lymphocyte (CTL) response against ovarian cancer cells. DNP conjugation may enhance the immunogenicity of weakly immunogenic antigens.
  • Autologous e6 t cell receptor genetically-modified t cells - A preparation of human autologous peripheral blood lymphocytes (PBLs) that have been genetically engineered to express a T-cell receptor (TCR) that specifically targets the viral oncoprotein human papillomavirus type 16 (HPV-16) E6, with potential antineoplastic activity. Upon administration, the HPV E6 TCR genetically-modified T-cells target and bind to HPV-16 E6-expressing tumor cells, which leads to specific cytotoxic T-lymphocyte (CTL)-mediated killing of HPV-16 E6-positive tumor cells. HPV-16 E6, a cell surface glycoprotein, plays a key role in the tumorigenesis of various HPV-associated tumors and is absent from healthy human tissues.
  • Autologous ebv-ctl cd19car zeta - Autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTL) that have been genetically modified to express a T-cell chimeric antigen receptor (CAR) targeting the CD19 antigen, with potential immunotherapeutic activity. The CAR consists of a single chain Fv of anti-CD19 IgG1 coupled with an intracellular signaling region of the zeta-chain of the TCR/CD3 complex (CD3 zeta). Autologous EBV-CTL CD19CAR zeta directs the T-lymphocytes to CD19-expressing tumor cells, stimulating a selective toxicity to tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
  • Autologous egfr-specific car-t-cells expressing anti-pd-1/ctla-4 antibodies - A preparation of autologous T-lymphocytes that have been activated and genetically modified to express immune checkpoint antibodies against the negative immunoregulatory receptors human cell surface receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4), and are transduced with a gene encoding a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) epidermal growth factor receptor (EGFR), with potential immunomodulating and antineoplastic activities. After isolation, activation, transduction, expansion in culture and reintroduction into the patient, the T-cells in the autologous EGFR specific CAR-T-cells expressing anti-PD-1/CTLA4 antibodies specifically target and kill EGFR-expressing tumor cells. The anti-PD-1 antibody secreted from the CAR-T cells binds to PD-1 expressed on T-cells and prevents the interaction of PD-1 with its ligand programmed cell death 1 ligand 1 (PD-L1, PD-1L1; CD274) expressed on cancer cells, which prevents PD-1-mediated signaling and T-cell exhaustion. The anti-CTLA4 expressed by the CAR-T cells targets and binds to CTLA4 expressed on T-cells, and inhibits the CTLA4-mediated downregulation of T-cell activation. Both antibodies enhance T-cell activation, improve immunosuppression in the tumor microenvironment (TME) and improve the T-cell mediated immune response against and toxicity in EGFR-expressing tumor cells. Both PD-1 and CTLA-4 negatively regulate T-cell activation and proliferation, and play a key role in immunosuppression within the TME. EGFR, a receptor tyrosine kinase that is overexpressed in a variety of cancer cell types, plays a key role in tumor cell proliferation.
  • Autologous egfrt/19-28z/4-1bbl car t-lymphocytes - Genetically modified autologous T-lymphocytes transduced with a replication incompetent retroviral vector expressing both tumor necrosis factor ligand superfamily (TNFSF) member 9 (TNFSF9; 4-1BBL) and a chimeric T cell antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment), fused to the extracellular, transmembrane and intracellular signaling domains of the T-cell co-stimulatory receptor CD28, the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) (19-28z), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous EGFRt/19-28z/4-1BBL CAR T-lymphocytes are directed to CD19-expressing tumor cells, which induces selective toxicity in CD19-expressing tumor cells. These cells also express 4-1BBL, a secreted protein and member of the TNFSF of growth factors, that induces proliferation of T-cells and may help reverse immunosuppression in the tumor environment. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The CD28 co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. The inclusion of the CD28 signaling domain may increase proliferation of T-cells and antitumor activity compared to the inclusion of the CD3-zeta chain alone. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.
  • Autologous epstein-barr virus-specific cytotoxic t lymphocytes - A preparation of lymphocytes harvested from a patient with an Epstein-Barr virus (EBV)-positive tumor. Ex vivo, the lymphocytes are activated against EBV-specific antigens and then returned to the patient, where they mount a specific immune response against EBV-positive tumor cells.
  • Autologous follicular lymphoma-derived idiotype vaccine - A patient-specific cancer vaccine directed against the soluble protein idiotype of an individual follicular lymphoma with potential antineoplastic activity. A patient-specific follicular lymphoma-derived anti-idiotype vaccine may be composed of a patient-specific, synthetic idiotype-related peptide (such as one corresponding to a hypervariable region of an IgG heavy chain) conjugated to the immunostimulant carrier protein keyhole limpet hemocyanin (KLH). Upon administration, this vaccine may induce an idiotype-specific cytotoxic T-lymphocyte (CTL) response against follicular lymphoma cells expressing the idiotype, resulting in tumor cell lysis.
  • Autologous fra-4scar-expressing t-cells 4scar-fra - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-folate receptor alpha (FRa; folate receptor 1; FOLR1) single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (CD3zeta; CD3z), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon administration, autologous FRa-4SCAR-expressing T-cells 4SCAR-FRa are directed to and induce selective toxicity in FRa-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. FRa is overexpressed in various tumor cell types, and is associated with increased leukemic cell proliferation and aggressiveness. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.
  • Autologous gamma-retroviral msgv1 139 scfv egfrviii car gene-modified t cells - A preparation of autologous T-lymphocytes transduced with the gamma retroviral vector MSGV1 expressing a chimeric T-cell antigen receptor (CAR) consisting of a single-chain variable fragment (scFv) from a specific antibody clone (mAb139) that targets a mutant form of epidermal growth factor receptor (EGFR) known as variant III (EGFRvIII; EGFR-vIII), with potential antineoplastic activity. Upon intratumoral administration, the gamma-retroviral MSGV1 139 scFv EGFRvIII CAR gene-modified T-cells specifically target and bind to tumor cells expressing EGFRvIII, leading to selective cytotoxicity in EGFRvIII-expressing tumor cells. EGFRvIII, a tumor-associated antigen (TAA) encoded by an in-frame deletion of exons 2-7 in the EGFR gene, is specifically overexpressed by a subset of tumor cells and is not expressed in normal, healthy cells. It plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance.
  • Autologous genetically-modified mage-a4 c1032 cd8alpha t cells - Autologous human T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the human melanoma antigen A4 (MAGE-A4) and the CD8alpha co-receptor, with potential immunostimulatory and antineoplastic activities. Upon leukapheresis, isolation, transduction, expansion ex vivo, and reintroduction into the patient, the autologous genetically-modified MAGE-A4 C1032 CD8alpha T-cells bind to tumor cells expressing MAGE-A4. This may result in both inhibition of growth and increased cell death of MAGE-A4-expressing tumor cells. The tumor-associated antigen MAGE-A4, a member of the MAGE-A family of cancer testis antigens, is overexpressed by a variety of cancer cell types. Co-expression of CD8alpha may broaden the immune response against tumors and increase antitumor activity by converting CD4+ helper T-cells into CD8+ cytotoxic T-cells.
  • Autologous genetically-modified mage-a4 c1032 t cells - Autologous human T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the human melanoma antigen A4 (MAGE-A4), with potential immunostimulatory and antineoplastic activities. Upon leukapheresis, isolation, transduction, expansion ex vivo, and reintroduction into the patient, the autologous genetically-modified MAGE-A4 C1032 T-cells bind to tumor cells expressing MAGE-A4. This may result in both inhibition of growth and increased cell death of MAGE-A4-expressing tumor cells. The tumor-associated antigen MAGE-A4, a member of the MAGE-A family of cancer testis antigens, is overexpressed by a variety of cancer cell types.
  • Autologous glioma cell lysate - A cell lysate derived from glioma cells with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the autologous glioma cell lysate exposes the immune system to an undefined amount of glioma-type tumor associated antigens (TAA), which may result in the induction of both specific anti-tumoral cytotoxic T lymphocytes (CTL) and antibody-dependent responses against the glioma TAA-expressing cells, resulting in glioma cell lysis.
  • Autologous gm-csf-secreting breast cancer vaccine - An autologous tumor cell vaccine containing irradiated breast cancer cells transfected with the granulocyte macrophage-colony-stimulating factor (GM-CSF) gene with potential antineoplastic activity. Autologous breast cancer cells are transduced ex vivo with an adenovirus vector encoding the GM-CSF gene and irradiated and then reintroduced into the patient. Upon repeated subcutaneous administration of the vaccine, autologous GM-CSF-secreting breast cancer cells secrete GM-CSF, which may stimulate a tumor-specific cytotoxic T-lymphocyte (CTL) response.
  • Autologous gm-csf-secreting lethally irradiated colorectal cancer cell vaccine - A lethally irradiated, autologous colorectal cancer vaccine consisting of patient-specific colorectal cancer cells genetically modified to secrete the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon vaccination, the autologous GM-CSF-secreting lethally irradiated colorectal cancer cell vaccine releases GM-CSF. In turn, GM-CSF may increase the body's immune response against tumor cells by promoting the maturation and activation of dendritic cells (DCs), and enhancing tumor-specific antigen presentation to both B- and T-cells, which leads to better recognition of tumors by the immune system. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
  • Autologous gm-csf-secreting lethally irradiated leukemia cell vaccine - An autologous cancer vaccine composed of lethally irradiated leukemia cells that are genetically modified to secrete the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon intradermal injection, the autologous GM-CSF-secreting lethally irradiated leukemia cell vaccine secretes GM-CSF. In turn, GM-CSF may stimulate the immune system to attack tumor cells by enhancing the activation of dendritic cells (DCs) and promoting antigen presentation to both B- and T-lymphocytes. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
  • Autologous gm-csf-secreting lethally irradiated lung cancer vaccine - An autologous lung cancer vaccine consisting of patient-specific lung cancer cells genetically modified to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), an immunostimulatory cytokine. GM-CSF modulates the proliferation and differentiation of a variety of hematopoietic progenitor cells with some specificity towards stimulation of leukocyte production and may reverse treatment-induced neutropenias. This agent also promotes antigen presentation, up-regulates antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function and may augment host antitumoral immunity. For safety, cells are irradiated prior to vaccination.
  • Autologous gm-csf-secreting lethally irradiated pancreatic cancer vaccine - An irradiated, autologous pancreatic cancer vaccine consisting of patient-specific pancreatic cancer cells genetically modified to secrete the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon vaccination, GVAX pancreatic cancer vaccine secretes GM-CSF. In turn, GM-CSF may stimulate the body's immune system against tumor cells by enhancing the activation of dendritic cells (DCs) and promoting antigen presentation to both B- and T-cells. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
  • Autologous gpc3/ny-eso-1/afp specific cd8-positive t-lymphocytes - A preparation of autologous CD8-positive T-lymphocytes that are exposed, ex vivo, to multiple specific hepatocellular carcinoma (HCC) antigens, including glypican (GPC)-3, New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and alpha-fetoprotein (AFP), with potential immunostimulating and antineoplastic activities. Upon infusion of the GPC3/NY-ESO-1/AFP-specific CD8-positive T lymphocytes, the T-cells specifically target and lyse cells expressing the targeted HCC neoantigens.
  • Autologous hbv-specific tcr-redirected t-lymphocytes - A preparation of human autologous T-lymphocytes transduced with a viral vector encoding for a T-cell receptor (TCR) specific for a human hepatitis B virus (HBV) surface antigen (HBsAg), with potential antineoplastic activity. Following administration, the autologous HBV antigen specific TCR-redirected autologous T-lymphocytes recognize and bind to the HBV antigen-positive cells, which induces cytotoxic T-lymphocyte (CTL)-mediated elimination of HBV antigen-positive cancer cells. HBV antigens are found on HBV-positive cells and HPV-induced hepatocellular carcinoma (HCC).
  • Autologous heat-shock protein 70 peptide vaccine ag-858 - A recombinant cancer vaccine made with tumor-derived heat shock protein 70 (HSP70) peptide complexes. HSP70 associates with antigenic peptides, transporting them into antigen presenting cells (APC) for processing. Tumor-derived HSP70-peptide complexes used in vaccine preparations have been shown to prime tumor immunity and tumor-specific T cells in animal models.
  • Autologous her2-car-modified adenovirus-specific cytotoxic t-lymphocytes - A population of autologous cytotoxic T-lymphocytes (CTLs) specifically reactive to human adenovirus (Ad) that have been transduced with a retroviral vector expressing a second-generation human epidermal growth factor receptor type 2 (HER2; EGFR2; ErbB2)-specific chimeric antigen receptor (CAR) comprised of an exodomain based on a anti-CD22 single chain variable fragment (scFv) from the anti-HER2 monoclonal antibody FRP5 that is linked to the costimulatory domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3zeta), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous HER2-CAR-modified Ad-specific CTLs are directed to and induce selective toxicity in HER2-expressing tumor cells. Additionally, these cells may help reconstitute Ad-specific CTL responses in immunocompromised individuals and others at risk of developing Ad-infection. HER2, a receptor tyrosine kinase (RTK) overexpressed by a variety of tumor cell types, belongs to the EGFR superfamily and plays a key role in tumor cell proliferation.
  • Autologous her2-specific/egfrt-expressing cd4/cd8-positive car t-cells - A preparation of CD4+ and CD8+ autologous T-lymphocytes transduced with a lentiviral vector expressing a human epidermal growth factor receptor type 2 (HER2; EGFR2; ErbB2)-specific chimeric antigen receptor (CAR) coupled to a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous HER2-specific/EGFRt-expressing CD4/CD8-positive CAR T-cells are directed to and induce selective toxicity in HER2-expressing tumor cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of these cells through an anti-EGFR antibody-induced antibody-dependent cellular cytotoxicity (ADCC) response. HER2, a receptor tyrosine kinase (RTK) overexpressed by a variety of tumor cell types, belongs to the EGFR superfamily and plays a key role in tumor cell proliferation.
  • Autologous hnscc dna-transfected semi-allogeneic fibroblasts mrc-5 vaccine - A vaccine consisting of lethally irradiated human fetal lung fibroblasts (Medical Research Council 5 or MRC-5) transfected with autologous tumor DNA derived from a head and neck squamous cell carcinoma (HNSCC), with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the autologous HNSCC DNA-transfected semi-allogeneic fibroblasts MRC-5 vaccine expresses HNSCC tumor-associated antigens (TAAs), which may activate the immune system to induce a cytotoxic T-lymphocyte (CTL) response against HNSCC cells. The MRC-5 cell line, established in 1966, is a human diploid lung fibroblast cell line derived from the human lung tissue of a 14-week-old male fetus.
  • Autologous hpv16 e7-specific hla-a*02:01-restricted tcr gene engineered lymphocytes kite-439 - A preparation of autologous T-lymphocytes that have been genetically modified to express a T-cell receptor (TCR) specific for the human leukocyte antigen (HLA)-A*02:01-restricted human papillomavirus type 16 isoform E7 protein (HPV16 E7) with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo and re-introduction into the patient, the autologous HPV16 E7-specific HLA-A*02:01-restricted T-lymphocytes KITE-439 target and bind HPV16 E7-expressing tumor cells. This may lead to cytotoxic T-lymphocyte (CTL)-mediated elimination of tumor cells expressing the HPV16 E7 antigen. HPV16 E7, a cell surface glycoprotein and tumor-associated antigen (TAA), is overexpressed in various HPV-mediated cancers.
  • Autologous hpv-16/18 e6/e7-specific tgf-beta-resistant t lymphocytes - A preparation of autologous transforming growth factor-beta (TGF-beta)-resistant cytotoxic T-lymphocytes (CTL) reactive to human papilloma virus (HPV) types 16 and 18 E6/E7 antigens, with potential antineoplastic activity. Autologous T-lymphocytes from a HPV-positive cancer patient are exposed to and stimulated with dendritic cells (DCs) loaded with the HPV-16/18 proteins E6 and E7. In turn, the HPV-16/18 E6/E7-specific T-lymphocytes are transduced with a retroviral vector expressing a dominant-negative mutant of type II transforming growth factor (TGF)-beta receptor, which blocks signaling mediated by all three TGF-beta isoforms. Following re-administration to patients with HPV-positive tumors, the HPV-16/18 E6/E7-specific TGF-beta-resistant T lymphocytes target HPV16/18 E6/E7-positive cells, which may result in a specific cytotoxic T-lymphocyte (CTL) response, followed by cell lysis and the inhibition of tumor cell proliferation. Tumors expressing TGF-beta inhibit T-lymphocyte activation and expansion.
  • Autologous hpv-specific cytotoxic t lymphocytes - A population of autologous cytotoxic T-lymphocytes (CTLs) that are specifically reactive to human papillomavirus (HPV), with potential antiviral and antineoplastic activities activities. Upon infusion of the autologous HPV-specific CTLs, these CTLs induce selective toxicity in HPV-positive cancer cells and other HPV-infected cells. HPV is associated with various cancer cell types.
  • Autologous ic9-deltangfr-cd19car-cd3zeta-4-1bb-expressing t-lymphocytes - A preparation of autologous T-lymphocytes that have been transduced with a retroviral vector to express a chimeric antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv) fused to a human immunoglobulin G1 (IgG1) hinge and a CD8alpha transmembrane domain, linked to the co-stimulatory molecule 4-1BB (CD137) and the cytoplasmic portion of the zeta chain of the human T-cell receptor (CD3zeta), containing the apoptosis-inducible suicide gene human caspase 9 (iCASP9 or iC9), linked to a drug binding domain, and a truncated low-affinity nerve growth factor receptor (deltaNGFR), with potential immunostimulating and antineoplastic activities. The iC9 construct consists of the sequence of the human FK506-binding protein (FKBP12) with an F36V mutation, connected through a Ser-Gly-Gly-Gly-Ser linker to the gene-encoding human caspase 9, which is deleted of its endogenous caspase activation and recruitment domain. Upon transfusion, the iCasp9-deltaNGFR-CD19CAR-CD3zeta-4-1BB-expressing autologous T-lymphocytes target and bind to CD19-expressing neoplastic B-cells. Prior to administration, deltaNGFR is used to select the CAR19-transduced T-cells for further enrichment by flow cytometry using an anti-NGFR antibody.
  • Autologous ic9-gd2car-cd28-cd3zeta-il-15-expressing t-lymphocytes - A preparation of autologous T-lymphocytes that have been transduced with the retroviral vector SFG, a Moloney murine leukemia (Mo-MuLV) virus-based vector, expressing both an extracellular domain consisting of interleukin 15 (IL-15) and a GD2-specific chimeric antigen receptor (CAR) derived from the monoclonal antibody 14G2a, linked to the CD28 and CD3zeta (TCRzeta; CD247) costimulatory signaling domains and containing the suicide gene, inducible caspase 9 (iCasp9 or iC9), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous iC9-GD2CAR-CD28-CD3zeta-IL-15-expressing T-lymphocytes recognize, bind to and induce selective cytotoxicity in GD2-expressing tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and potentiates the immune response against tumor cells. Incorporation of the costimulatory signaling domains increases T-cell function, expansion, and survival. The iCasp9 safety switch consists of a full-length caspase 9, including its caspase recruitment domain, linked to a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V). If the administered CAR T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903, which binds to the FKBP12-F36V drug-binding domain, activates caspase 9 and results in apoptosis of the administered CAR T-cells, can be administered. GD2, a disialoganglioside and tumor-associated antigen (TAA), is overexpressed on the surface of neuroblastoma cells and other neuroectoderm-derived neoplasms and is minimally expressed on normal, healthy cells.
  • Autologous ic9-gd2-car-expressing vzv-specific t lymphocytes - Genetically modified, autologous varicella zoster virus (VZV)-specific T-lymphocytes transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for the disialoganglioside GD2, which contains the signaling domains for the co-stimulatory molecules CD28 and CD134 (OX-40), and the suicide gene, inducible caspase 9 (iCasp9 or iC9), with potential immunomodulating and antineoplastic activities. Upon intravenous administration, iC9-GD2-CD28-OX40-expressing T lymphocytes target the GD2 antigen on tumor cells for selective toxicity against GD2-expressing tumor cells. iCasp9 consists of a full-length caspase 9, including its caspase recruitment domain, linked to a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V). If the administered T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered, which binds to the FKBP12-F36V drug binding domain, activates caspase 9, and results in apoptosis of the administered T-cells. Expression of the iCasp9 gene in T cells for adoptive transfer increases safety and broadens the scope for their clinical applications. The tumor associated antigen GD2 is overexpressed on the surface of almost all tumors of neuroectodermal origin. OX40 and CD28, both T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation. An additional VZV vaccine can be administered to increase T-cell activity.
  • Autologous icasp9-cd19-expressing t-lymphocytes - A preparation of autologous T-lymphocytes that are transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD19 and the inducible suicide gene human caspase 9 (iCASP9 or iC9), that is linked to a drug binding domain, with potential immunomodulating and antineoplastic activities. The iCASP9 construct consists of the entire coding sequence for the human FK506-drug binding protein (FKBP12) with an F36V mutation (FKBP12-F36V) that is linked to the gene encoding iC9, which is a modified form of the CASP9 gene where the sequences encoding the endogenous caspase activation and recruitment domains have been deleted. Upon intravenous administration, autologous iCASP9-CD19-expressing T-lymphocytes (iC9-CAR19 T-cells) target and bind to CD19-expressing tumor cells, thereby selectively lysing these tumor cells. If the administered T-cells cause unacceptable side effects, the chemical homodimerizer AP1903, which binds to the FKBP12-F36V drug-binding domain, can be administered; this induces caspase 9 expression, and results in apoptosis of the administered iC9-CAR19 T-cells. The CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
  • Autologous icasp9-deltangfr-cd19car-expressing t cells - A preparation of autologous T-lymphocytes that are transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for the CD19 antigen, the suicide gene, inducible human caspase 9 (iCasp9 or iC9), and a truncated low-affinity nerve growth factor receptor (deltaNGFR), with potential immunomodulating and antineoplastic activities. The iCasp9 construct consists of the entire coding sequence for the human FK506-drug binding protein (FKBP12) with an F36V mutation (FKBP12-F36V) that is linked to the gene encoding human caspase 9, which is deleted of its endogenous caspase activation and recruitment domains. Upon intravenous administration, autologous iCasp9-deltaNGFR-CD19CAR-expressing T cells are selectively toxic to CD19-expressing tumor cells. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered, which binds to the FKBP12-F36V drug binding domain, activates caspase 9, and results in apoptosis of the administered CAR19 T-cells. The CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Prior to administration, deltaNGFR, is used to select the CAR19-transduced T-cells for further enrichment by flow cytometry using an anti-NGFR antibody.
  • Autologous il-21-modulated cd8+ mart1-specific t cells - A preparation of interleukin 21 (IL-21) stimulated, CD8+ T-lymphocytes sensitized to MART-1 (melanoma antigen recognized by T-cells) antigen with potential immunostimulating and antineoplastic activities. CD8+ T-lymphocytes are exposed ex vivo to autologous dendritic cells (DCs) pulsed with MART-1 antigen peptide and grown in the presence of IL-21. These tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the MART-1 antigen, resulting in tumor cell lysis. MART-1 is expressed by certain types of melanoma cells. IL-21, a cytokine involved in the regulation of cellular immune responses, may play a key role during priming of antigen-specific CD8+ T cells and may enhance proliferation of the CTLs.
  • Autologous il-2-expressing b-cll vaccine - A cancer vaccine consisting of autologous, B-chronic lymphocytic leukemia (B-CLL) cells harvested from a patient and transduced ex vivo with an adenoviral vector encoding the gene for the human cytokine interleukin-2 (IL-2), with potential immunostimulating and antineoplastic activities. Upon reintroduction into the patient, the autologous IL-2-expressing B-CLL vaccine expresses IL-2, stimulates natural killer (NK) cells, and may enhance the cytotoxic T-lymphocyte (CTL) immune response against the patient's B-CLL cells.
  • Autologous immunoglobulin idiotype-klh conjugate vaccine - A cancer vaccine composed of tumor-specific idiotype determinants derived from an individual's tumor cells which are conjugated to keyhole limpet hemocyanin, an immunostimulant carrier protein. When injected into the individual from whom the tumor cells were isolated, this vaccine may stimulate an antitumoral cytotoxic T-lymphocytic immune response.
  • Autologous interferon-producing killer dendritic cells - A preparation of autologous dendritic cells (DC) with a molecular expression profile similar to both natural killer (NK) cells and DCs, with potential antineoplastic activity. Autologous interferon-producing killer dendritic cells (IKDCs) are characterized by double-negative expression of CD3 and CD19; these cells also express low levels of CD11 and are positive for B220. They are distinguished from plasmacytoid DCs (pDCs) by the absence of lymphocyte antigen 6C (Ly6C, Gr-1) expression. IKDCs produce interferon gamma (IFN-gamma) and interleukin (IL) -12, and are able to kill typical NK target cells using NK receptors while retaining DC-like antigen-presenting activity. Upon administration of the autologous IKDCs, these cells secrete high levels of IFN-gamma and, when in contact with tumor cells, mediate TNF-related apoptosis-inducing ligand (TRAIL)-dependent direct lysis of tumor cells. The resulting apoptotic tumor antigens may be presented by the IKDCs, thus activating the immune system to exert a cytotoxic T-lymphocyte (CTL) response to further eliminate tumor cells.
  • Autologous lmp1-/lmp2- specific cytotoxic t-lymphocytes - A preparation of cytotoxic T-lymphocytes (CTL), specifically reactive to the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and 2, with potential antineoplastic activity. Autologous dendritic cells and EBV-infected lymphoblastoid cell lines (LCL) from patients with EBV-positive nasopharyngeal carcinoma (NPC) are transduced with an LMP1/LMP2-expressing adenoviral vector, are irradiated, and then are used to stimulate and expand autologous CTL to produce autologous LMP1-/LMP2-specific CTL ex vivo. Administration of autologous LMP1-/LMP2- specific cytotoxic T-lymphocytes may result in a specific CTL response against tumor cells expressing LMP1 and LMP2, resulting in cell lysis and inhibition of tumor cell proliferation in vivo. Among a limited set of viral antigens expressed by NPC cells, LMP1 and LMP2 are weak immunogens which, nevertheless, are capable of inducing a T-lymphocyte response.
  • Autologous lmp1/lmp2/ebna1-specific hla-a02:01/24:02/11:01-restricted tcr-expressing t-lymphocytes yt-e001 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector encoding a T-cell receptor (TCR) specific for human leukocyte antigen (HLA)-A02:01/24:02/11:01-restricted Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and 2, and EBV nuclear antigen 1 (EBNA1), with potential antineoplastic activity. Upon administration, the autologous LMP1/LMP2/EBNA1-specific, HLA-A02:01/24:02/11:01-restricted TCR-expressing T-lymphocytes YT-E001 recognize and bind to HLA-presented EBV peptides, which may promote cell death and inhibit the growth of tumor cells expressing LMP1, LMP2 or EBNA1. LMP1, LMP2, and EBNA1 are expressed in various, EBV-associated malignancies, including nasopharyngeal cancer and EBV-positive Hodgkin lymphoma.
  • Autologous lymphoid effector cells specific against tumor cells - A preparation of cytotoxic, autologous lymphoid effector cells specifically targeted towards tumor cells, with potential immunomodulating and antineoplastic activities. The autologous lymphoid effector cells are prepared by drawing a blood sample containing the required precursors for CD4+ helper T-cells, CD8+ cytotoxic T-cells, and natural killer (NK) cells from a cancer patient. The precursor cells are activated, selected and expanded to generate mature autologous lymphoid effector cells with the potential for enhanced tumor recognition. Upon readministration into the patient, the autologous lymphoid effector cells may induce both humoral and cellular immune responses against tumor cells. This may result in the immune-mediated inhibition of tumor cell proliferation, which leads to tumor cell death.
  • Autologous lymphoma cell lysate-pulsed autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysate from autologous lymphoma cells with potential immunostimulatory and antineoplastic activities. Upon intranodal administration, autologous lymphoma cell lysate-pulsed autologous DC vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against lymphoma cells, which may result in lymphoma cell lysis.
  • Autologous lymphoma cell/allogeneic dendritic cell electrofusion hybrid vaccine - A cell-based cancer vaccine consisting of hybrid cells created by electrofusing allogeneic dendritic cells (DCs) and autologous lymphoma cells with potential immunostimulating and antitumor activities. Upon administration, autologous lymphoma cell/allogeneic dendritic cell electrofusion hybrid vaccine may stimulate the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against specific autologous lymphoma-associated antigens, resulting in lymphoma cell apoptosis.
  • Autologous lymphoma cell/autologous dendritic cell electrofusion hybrid vaccine - A cell-based cancer vaccine consisting of hybrid cells created by electrofusing autologous dendritic cells (DCs) and autologous lymphoma cells with potential immunostimulating and antitumor activities. Upon administration, autologous lymphoma cell/autologous dendritic cell electrofusion hybrid vaccine may stimulate the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against specific autologous lymphoma-associated antigens, resulting in lymphoma cell apoptosis.
  • Autologous lymphoma immunoglobulin-derived scfv-chemokine dna vaccine - A plasmid DNA vaccine encoding an autologous lymphoma-derived idiotype-targeting immunoglobulin (Ig)-derived single chain variable fragment (scFv) fused to the chemokine macrophage inflammatory protein 3 alpha (MIP3a), with potential immunostimulating and antineoplastic activities. Upon intramuscular vaccination, the autologous lymphoma immunoglobulin-derived scFv-chemokine DNA vaccine is taken up by antigen-presenting cells (APCs) and stimulates the immune system to exert a cytotoxic T-lymphocyte (CTL) response against the idiotype expressed on the surface of B lymphoma cells. MIP3a, also called chemokine (C-C motif) ligand 20 (CCL20), is a chemotactic cytokine able to enhance the immune response through binding to chemokine receptors expressed on APCs.
  • Autologous mage-a10-specific hla-a2-restricted tcr c796 gene-engineered lymphocytes - Human autologous T-lymphocytes transduced with a retroviral vector encoding a high-affinity T-cell receptor (TCR) specific for human leukocyte antigen (HLA)-A2-restricted, human melanoma-associated antigen A10 (MAGE-A10), clone 796 (c796), with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMCs) are isolated from a patient, transduced with an anti-MAGE-A10(c796)-HLA-A2 restricted TCR, expanded ex vivo, and reintroduced into the HLA-A2-positive patient. Upon reintroduction, the autologous MAGE-A10-specific, HLA-A2-restricted TCR c796 gene-engineered lymphocytes bind to tumor cells expressing the MAGE-A10 antigen, which may induce cell death in and halt the growth of MAGE-A10-expressing cancer cells. The tumor-associated antigen MAGE-A10, a member of the MAGE-A family of cancer/testis tumor-associated antigens (CT-TAAs), is overexpressed by a variety of cancer cell types.
  • Autologous mage-a3/a6-specific tcr gene-engineered lymphocytes kite-718 - Human autologous T-lymphocytes genetically modified to express a T-cell receptor (TCR) that specifically targets human melanoma-associated antigen A3 (MAGE-A3) and MAGE-A6 (MAGEA3/A6; MAGE-A3/A6), with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMCs) are isolated from a patient, transduced with a gene expressing a TCR specific for the MAGE-A3/A6 antigens, expanded ex vivo, and reintroduced into the patient. Then, the autologous MAGE-A3/A6-specific TCR gene engineered lymphocytes KITE-718 target and bind to tumor cells expressing the MAGE-A3 and/or MAGE-A6 antigens. This halts the growth of and kills MAGE-A3/A6-expressing cancer cells. The tumor-associated antigens MAGE-A3 and MAGE-A6 are overexpressed on a variety of tumor cell types.
  • Autologous mage-a3-specific hla-a*01-restricted t cell receptor gene engineered lymphocytes - Human autologous T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the human leukocyte antigen (HLA)-A*01-restricted, human melanoma-associated antigen A3 (MAGE-A3), with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMCs) are isolated from a patient, transduced with an anti-MAGE-A3-HLA-A*01 restricted TCR, expanded ex vivo, and reintroduced into the HLA-A*01-positive patient. Then, the autologous MAGE-A3-specific, HLA-A*01-restricted TCR gene engineered lymphocytes bind to tumor cells expressing the MAGE-A3 antigen, which may increase cell death and halt the growth of MAGE-A3-expressing cancer cells. The tumor-associated antigen MAGE-A3 is overexpressed by a variety of cancer cell types.
  • Autologous mcpyv-specific hla-a02-restricted tcr-transduced cd4+ and cd8+ t-cells fh-mcva2tcr - A preparation of autologous CD4+ and CD62L-expressing CD8+ T-cells transduced with a third generation lentiviral vector (LV) to express the high affinity T-cell receptor (TCR) A2 -MCC1, specific for the human leukocyte antigen (HLA)-A02-restricted Merkel cell polyomavirus (MCPyV; MCV) viral oncoprotein, with potential immunomodulating and antineoplastic activities. Upon reintroduction into the patient, the autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD8+ and CD4+ T-cells FH-MCVA2TCR selectively bind to the KLLEIAPNC epitope (KLL epitope) within the MCPyV viral oncoprotein. This results in cytotoxic T-lymphocyte (CTL)-mediated elimination of tumor cells expressing the MCPyV viral oncoprotein. Additionally, tumor-specific HLA-A02-restricted CD4+ cells promote class I-restricted CD8+ proliferation, survival and effector functions by producing interleukin (IL)-2 and facilitating the activation of dendritic cells (DCs). MCPyV viral oncoprotein is highly expressed in Merkel cell carcinoma (MCC) caused by MCPyV.
  • Autologous mdc3 vaccine - An antineoplastic vaccine composed of autologous mature dendritic cells (mDCs) pulsed with mutated peptides, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous mDC3 vaccine may elicit a cytotoxic T-cell (CTL) response against cancer cells.
  • Autologous mdc3/8-kras vaccine - An antineoplastic vaccine composed of autologous mature dendritic cells (mDCs) pulsed with mutant KRAS peptides specific to a patient's tumor mutation and human leukocyte antigen (HLA) type, with potential immunostimulating and antineoplastic activities. Upon administration, this vaccine, which is administered as an mDC3 primer, followed by an mDC8 booster, may elicit a cytotoxic T-cell (CTL) response against cancer cells expressing certain KRAS mutations. K-RAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutation of K-RAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis.
  • Autologous melanoma lysate/klh-pulsed autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysate from autologous melanoma cells containing tumor associated antigens (TAAs) and conjugated to the immunostimulant Keyhole limpet hemocyanin (KLH), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous melanoma lysate/KLH-pulsed autologous dendritic cell vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against melanoma cells, which may result in melanoma cell lysis. KLH is an immunogenic carrier and serves as an immunostimulant to improve antigenic immune recognition and T-cell responses and can be used to evaluate vaccine efficacy.
  • Autologous melanoma lysate/ny-eso-1-pulsed autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with both a lysate from autologous melanoma cells containing tumor associated antigens (TAAs) and a synthetic peptide derived from the tumor associated antigen human cancer-testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon administration, autologous melanoma lysate/NY-ESO-1-pulsed autologous DC vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody-mediated immune responses against melanoma cells, which may result in melanoma cell lysis. NY-ESO-1 is expressed in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.
  • Autologous melanoma lysate-pulsed autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysate from autologous melanoma cells containing tumor associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, autologous melanoma lysate-pulsed autologous DC vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against melanoma cells, which may result in melanoma cell lysis.
  • Autologous mesenchymal stem cells apceth_101 - Human autologous mesenchymal stem cells (MSCs) harvested from the bone marrow of a patient and genetically modified with a self-inactivating retroviral vector expressing the suicide gene herpes simplex virus thymidine kinase (HSV-TK), that can be used to activate synthetic acyclic guanosine analogues when co-administered. Upon intravenous administration of autologous mesenchymal stem cells apceth_101, the cells are actively recruited to the tumor stroma, differentiate into more mature mesenchymal cells, and become part of the tumor microenvironment. When a synthetic acyclic guanosine analogue, such as ganciclovir, is co-administered, the HSV-TK within the HSV-TK-transduced MSCs will monophosphorylate this prodrug. Subsequently the monophosphate form is further converted to the diphosphate form and then to its active triphosphate form by cellular kinases. The active form of ganciclovir kills the HSV-TK-transduced MSCs and leads to a bystander effect, which eliminates neighboring cancer cells. Therefore, synthetic acyclic guanosine analogues are activated only at the tumor site, which increases their local efficacy and reduces systemic toxicity.
  • Autologous mesothelin-specific car-t cells - Genetically modified, autologous T-lymphocytes transduced with a gene encoding a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) mesothelin, with potential immunomodulating and antineoplastic activities. After isolation, transduction, expansion in culture, and reintroduction into the patient, the autologous mesothelin-specific CAR-T cells specifically target and kill mesothelin-expressing tumor cells. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types.
  • Autologous mesothelin-specific car-t-cells expressing anti-pd-1/ctla-4 antibodies - A preparation of autologous, engineered T-lymphocytes that express both a second-generation chimeric antigen receptor (CAR) specific for the human gastric carcinoma-associated antigen MG7, and the co-stimulatory molecule 4-1BB (CD137), with potential antineoplastic activity. Upon intratumoral injection, the autologous anti-MG7-CAR T-lymphocytes target and attach to cancer cells expressing MG7. This induces selective toxicity in and causes lysis of MG7-expressing tumor cells. MG7, a glycosylated protein sequence from the tumor-associated antigen (TAA) carcinoembryonic antigen (CEA), plays a key role in the development of certain tumor cell types. 4-1BB enhances T-cell activation and signaling after recognition of MG7.
  • Autologous mesothelin-specific human mrna car-transfected pbmcs mcy-m11 - Autologous peripheral blood mononuclear cells (PBMCs) transfected with anti-mesothelin chimeric antigen receptor (CAR) mRNA, with potential antineoplastic activity. Upon intraperitoneal (IP) administration, the autologous mesothelin-specific human mRNA CAR-transfected PBMCs MCY-M11 recognize, bind to, phagocytose and directly kill cancer cells expressing mesothelin. In addition, MCY-M11 stimulates the immune system to induce a cytotoxic T-lymphocyte response against the mesothelin-expressing cancer cells. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in many epithelial-derived cancers.
  • Autologous monocyte-derived lysate-pulsed dendritic cell vaccine pv-001-dc - A cell-based cancer vaccine composed of autologous, monocyte-derived dendritic cells (mDCs) pulsed with tumor cell lysate containing tumor associated antigens (TAAs), with potential immunostimulatory and antineoplastic activities. Upon administration,the autologous tumor cell lysate-pulsed mDCs vaccine PV-001-DC may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the patient's tumor cell-specific TAAs, which may result in tumor cell lysis.
  • Autologous mrna-modified anti-cmet car-t cells - A preparation of autologous, genetically-engineered T-lymphocytes that have been electroporated with an mRNA encoding a chimeric antigen receptor (CAR) consisting of an anti-human hepatocyte growth factor receptor (HGFR or cMET) single chain variable fragment (scFv), with potential antineoplastic activities. Upon administration, autologous mRNA-modified anti-cMET CAR-T cells direct T-cells to cMET-expressing tumor cells, which induces selective toxicity against cMET-expressing tumor cells and causes tumor cell lysis. cMET, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.
  • Autologous multi-lineage potential cells - A preparation of autologous multi-lineage potential cells (AMPC) which were induced to de-differentiate from somatic leukocytes from peripheral blood, with potential immunomodulating and antineoplastic activities. Upon introduction into the patient, the AMPC may help replace the abnormal cells in the body to create healthy bone marrow in the treatment of acute myeloid leukemia (AML).
  • Autologous natural killer cell-like ctls - A preparation of cytotoxic T-lymphocytes (CTLs) that express natural killer (NK)-like features (nCTLs), with potential immunomodulating and antineoplastic activities. The nCTLs are derived from autologous lymphocytes that have been in vitro exposed to autologous alpha-type-1 polarized dendritic cells that are pulsed with specific autologous tumor-associated antigens (TAAs); the nCTLs are subsequently expanded in the presence of the cytokine human interleukin-2 (IL-2). The generated nCTLs are potent CTLs that produce high amounts of granzyme B and perforin, and interferon-gamma (IFNg) with high killer activity and tumor-homing potential. Upon infusion of the autologous nCTLs, these cells specifically recognize the TAAs on the tumor cells, then bind to and directly lyse tumor cells.
  • Autologous nectin-4/fap-targeted car-t cells - A preparation of autologous T-lymphocytes engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) nectin-4 and cell surface protein fibroblast activation protein (FAP), and additionally an inducible expression cassette encoding transgenic interleukin (IL) 7 (IL-7) or 12 (IL-12), with potential immunostimulating and antineoplastic activities. Upon intratumoral administration, the autologous nectin-4/FAP-targeted CAR-T cells target and bind to nectin-4-expressing tumor cells and FAP-expressing cancer associated fibroblasts (CAFs). This results in a cytotoxic T-lymphocyte (CTL) response against nectin-4-expressing tumor cells and FAP-expressing CAFs, leading to cell lysis of these cells. Upon the binding to nectin-4 and FAP and the activation of the CAR-T cells, cytokine IL-7 or IL-12 is also released. This further augments the immune responses against the tumor cells, which may include the attack of nectin-4-negative tumor cells by tumor necrosis factor alpha (TNFa). Nectin-4, a TAA belonging to the nectin family, is overexpressed in a variety of cancers, including breast, bladder, lung and pancreatic cancer. FAP, a cell surface glycoprotein, is overexpressed on CAFs but minimally expressed on normal, healthy cells.
  • Autologous neuroblastoma lysate/klh-pulsed dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with a cell lysate from an autologous neuroblastoma containing tumor-associated antigens (TAAs) and the immunostimulant keyhole limpet hemocyanin (KLH), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous neuroblastoma lysate/KLH-pulsed DC vaccine may stimulate the immune system to mount an anti-tumoral cytotoxic T-lymphocyte (CTL) response against neuroblastoma cells, which may result in tumor cell lysis. KLH is an immunogenic carrier and serves as an immunostimulant to improve antigenic immune recognition and T-cell responses.
  • Autologous nkg2d car t-cells cyad-02 - A preparation of autologous T-lymphocytes that have been genetically modified and transduced with a retroviral vector to co-express a chimeric antigen receptor (CAR) encoding human natural-killer group 2, member D receptor protein (NKG2D or KLRK1) with a short hairpin RNA (shRNA) targeting MHC class I chain-related protein A (MICA) and MICB, with potential immunostimulating and antineoplastic activities. Upon infusion back into the patient, autologous NKG2D CAR T-cells CYAD-02 specifically recognize and bind to tumor cells expressing NKG2D ligands, resulting in the lysis of NKG2D ligand-expressing tumor cells. In addition, CYAD-02 targets, binds to and kills NKG2D ligand expressing tumor-associated endothelial cells in the neovasculature and immunosuppressive cells, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) that express NKG2D ligands. It also activates macrophages within the TME. Ligands for NKG2D, such as MICA, MICB, and members of the UL16-binding proteins (ULBP)/retinoic acid early transcript 1 (RAET1) family, are overexpressed on infected cells and most cancer cell types, but are not expressed on most normal, healthy cells. NKG2D, a dimeric, type II transmembrane protein expressed on human natural killer (NK) and certain T-cells, in association with the natural adaptive protein DAP10, promotes the elimination of NKG2D ligand-expressing cells. The shRNA downregulates the expression of MICA and MICB on the CAR-T cells, which increases in-vitro cell expansion. This may enhance their persistence and increase anti-tumor activity.
  • Autologous nkg2d car-cd3zeta-dap10-expressing t-lymphocytes cyad-01 - A preparation of autologous peripheral blood T-lymphocytes (PBTLs) that have been genetically modified and transduced with a retroviral vector to express a chimeric antigen receptor (CAR) encoding full-length human natural-killer group 2, member D receptor protein (NKG2D or KLRK1) fused to the CD3zeta cytoplasmic signaling domain and containing the naturally-expressed adaptor molecule DNAX-activating protein of 10 kDa (DAP10), with potential immunostimulating and antineoplastic activities. Upon infusion back into the patient, autologous NKG2D CAR-CD3zeta-DAP10-expressing T-lymphocytes CYAD-01 specifically recognize and bind to tumor cells expressing NKG2D ligands. This induces secretion of pro-inflammatory cytokines and results in the lysis of NKG2D ligand-expressing tumor cells. In addition, CYAD-01 targets, binds to and kills NKG2D ligand expressing tumor-associated endothelial cells in the neovasculature and immunosuppressive cells, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) that express NKG2D ligands. It also activates macrophages within the TME. Ligands for NKG2D, such as MHC class I chain-related protein A (MICA), MICB, and members of the UL16-binding proteins (ULBP)/retinoic acid early transcript 1 (RAET1) family, are overexpressed on infected cells and most cancer cell types, but are not expressed on most normal, healthy cells. NKG2D, a dimeric, type II transmembrane protein expressed on human natural killer (NK) and certain T-cells, in association with the natural adaptive protein DAP10, promotes the elimination of NKG2D ligand-expressing cells. The CD3zeta signaling domain and DAP10 provide co-stimulatory signaling upon ligand binding, enhance the secretion of pro-inflammatory cytokines in response to binding to NKG2D ligand-expressing tumor cells and enhances T-cell cytotoxicity. DAP10 also associates with and stabilizes NKG2D, which facilitates expression of the NKG2D-CAR-CD3zeta construct at the cell surface.
  • Autologous nsclc dna-transfected semi-allogeneic fibroblasts mrc-5 vaccine - A vaccine consisting of irradiated human fetal lung fibroblasts (Medical Research Council 5 or MRC-5) transfected with autologous non-small cell lung cancer (NSCLC)-derived DNA with potential immunostimulatory and antineoplastic activities. Upon administration, autologous NSCLC DNA-transfected semi-allogeneic fibroblasts MRC-5 vaccine expresses NSCLC tumor-associated antigens (TAAs) in addition to MHC class I-determinants and the co-stimulatory molecule B7.1, which may induce a cytotoxic T-lymphocyte (CTL) response against NSCLC cells. The MRC-5 cell line is a human diploid lung fibroblast cell line extablished in 1966.
  • Autologous nsclc peptide-specific dendritic cell vaccine - A personalized cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with immunogenic peptides derived from autologous non-small cell lung cancer (NSCLC) cells, with potential immunostimulating and antineoplastic activities. During leukapheresis, mature DCs are loaded with autologous NSCLC-derived peptides. Upon re-administration of the NSCLC peptide-specific DC vaccine, the immune system is exposed to NSCLC-associated antigens. This results in the induction of a specific cytotoxic T-lymphocyte (CTL) response against NSCLC cells and tumor cell lysis.
  • Autologous ny-eso-1 tcr-targeted t lymphocytes - A preparation of human autologous T-lymphocytes that are transduced with a gene encoding a T-cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1, with potential immunostimulating and antineoplastic activities. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the anti-NY-ESO-1 TCR-transduced autologous T-cells recognize and bind to NY-ESO-1-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of NY-ESO-1-positive tumor cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types, and is not, or is minimally, expressed in normal, healthy cells.
  • Autologous ny-eso-1-melanoma-specific cd8+ t-lymphocytes - A preparation of autologous CD8+ (cytotoxic) T-lymphocytes sensitized to cancer-testis antigen NY-ESO-1 antigen with potential immunostimulating and antineoplastic activities. Autologous CD8+ T-lymphocytes, isolated from a melanoma patient, are exposed to an NY-ESO-1 peptide ex vivo, expanded, and reintroduced into the patient; these tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1, an antigen found in normal testis, may be upregulated in various cancers, including bladder, breast, hepatocellular, melanoma, and prostate cancers.
  • Autologous ny-eso-1-redirected crispr-edited t cells - A preparation of human autologous T-lymphocytes that are transduced with a lentiviral vector (LV) encoding a T-cell receptor (TCR) specific for the tumor-associated antigen (TAA) cancer-testis antigen NY-ESO-1 and gene-edited with the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease complex to eliminate endogenous TCR and programmed cell death 1 (PD-1) expression, with potential immunostimulating and antineoplastic activities. The CRISPR guide RNA (gRNA) specifically targets and binds to complementary sites on TCRalpha, TCRbeta and PD-1. In turn, Cas9 cleaves these specific DNA sites, thereby disrupting transcription. Upon isolation, transduction, electroporation with TCRalpha, TCRbeta and PD-1 gRNAs which are complexed to Cas9 RNA to disrupt expression of endogenous TCRalpha, TCRbeta and PD-1, expansion ex vivo, and reintroduction into the patient, the anti-NY-ESO-1 TCR LV-transduced CRISPR-edited autologous T-cells recognize and bind to NY-ESO-1-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of NY-ESO-1-positive tumor cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types, and is not, or is minimally, expressed in normal, healthy cells. PD-1, an immune checkpoint receptor expressed on T-cells, plays a key role in tumor immune evasion by binding to its ligand programmed cell death ligand 1 (PD-L1) expressed on tumor cells. By removing PD-1 from T-cells, PD-1-mediated signaling is halted which may decrease T-cell exhaustion and may enhance T-cell activity against the NY-ESO-1-expressing tumor cells. Removal of endogenous TCR reduces TCR competition for expression, increases the persistence and function of the expressed transgenic TCR, enhances resistance to T-cell exhaustion and increases T-cell activity.
  • Autologous ny-eso-1-specific cd8-positive t lymphocytes - A preparation of autologous CD8+ T-lymphocytes specifically reactive to the cancer-testis antigen NY-ESO-1, with potential immunostimulating and antineoplastic activities. Autologous NY-ESO-1-specific CD8+ T-lymphocytes were generated from T-cells isolated from a particular cancer patient, which were made specifically reactive to the NY-ESO-1 antigen, expanded ex vivo, and reintroduced into the patient. These tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1, an antigen found in normal testis, may be upregulated in various cancers.
  • Autologous ofa-ilrp rna-transfected dendritic cell vaccine - A cancer vaccine consisting of autologous, mature monocyte-derived dendritic cells (DCs) transfected with oncofetal antigen immature laminin receptor protein (OFA-iLRP) RNA, with potential antineoplastic activity. Upon administration, DCs in the OFA-iLRP RNA-transfected autologous dendritic cell vaccine express, process, and present OFA-iLRP to the host immune system, which may mount a potent cytotoxic T-cell (CTL) response against OFA-iLRP-expressing tumor cells. As a highly conserved protein, OFA-iLRP is preferentially expressed in fetal tissues and in many types of cancer, including hematopoietic malignancies, but is not detectable in normal differentiated adult cells.
  • Autologous ovarian cancer immunogene-modified t lymphocytes - A preparation of autologous immunogene modified T-lymphocytes (IgT) that have been genetically engineered to be specifically reactive to ovarian cancer (OC) cells, with potential antineoplastic and immunostimulating activities. Upon administration of the autologous OC-IgT cells, the T-cells recognize and induce specific toxicity in the OC cells.
  • Autologous ovarian cancer-specific cytotoxic t-lymphocytes - A preparation of autologous cytotoxic T-lymphocytes (CTLs) genetically modified to target a not yet disclosed ovarian cancer-specific tumor-associated antigen (TAA), with potential immunomodulating and antineoplastic activities. After isolation, transduction, expansion in culture, and reintroduction into the patient, the autologous ovarian cancer-specific cytotoxic T-lymphocytes (OC-CTLs) bind to and induce selective toxicity in tumor cells expressing the TAA.
  • Autologous ovarian tumor cell lysate-pulsed dendritic cell vaccine - A cell-based cancer vaccine composed of autologous, irradiated dendritic cells (DCs) pulsed with ovarian tumor cell lysate containing tumor associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, autologous ovarian tumor cell lysate-pulsed dendritic cell vaccine may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against ovarian tumor cells expressing the patients ovarian tumor cell-specific TAAs, which may result in ovarian tumor cell lysis.
  • Autologous oxidized ovarian tumor cell lysate vaccine - An autologous cancer vaccine composed of oxidized ovarian tumor cell lysate, with potential immunostimulatory and antineoplastic activities. Upon administration, the autologous oxidized ovarian tumor cell lysate vaccine exposes the immune system to an undefined amount of tumor-associated antigens (TAAs), which may result in the induction of both anti-tumor cytotoxic T-lymphocytes (CTLs) and antibody-dependent responses against TAA-expressing cells, leading to tumor cell lysis. Compared to non-oxidized tumor cell lysate vaccines, oxidized tumor cell lysate vaccines induce necrotic cell death, increase the immunogenicity of the TAAs and may enhance the anti-tumor immune response.
  • Autologous pancreatic adenocarcinoma lysate and mrna-loaded dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) loaded with pancreatic adenocarcinoma lysate and mRNA containing and encoding tumor associated antigens (TAAs), with potential immunostimulatory and antineoplastic activities. Upon administration by perinodal injection using ultrasound guidance, the autologous pancreatic adenocarcinoma lysate and mRNA-loaded DC vaccine may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the patient's tumor cell-specific TAAs, which may result in tumor cell lysis.
  • Autologous pbls retrovirally-transduced with tcrs targeting neoantigens - Autologous human peripheral blood lymphocytes (PBLs) transduced with a retroviral vector encoding T-cell receptors (TCRs) specific for a patient's individual and unique mutated antigens, with potential immunostimulating and antineoplastic activities. Tumor cells are analyzed to identify and isolate specific mutated tumor-associated antigens (TAAs) that are expressed by the patient's tumor cells; then T-cell receptor coding sequences are engineered to target the patient's TAAs and inserted into retroviral vectors. After transduction, expansion in culture, and reintroduction into the patient, neoantigen-specific TCRs retroviral vector-transduced autologous PBLs recognize and bind to tumor cells expressing the patient's neoantigens, which results in a specific cytotoxic T-lymphocyte (CTL)-mediated immune response against the patient's tumor cells.
  • Autologous pbtl cd19car-28 zeta - A preparation of autologous peripheral blood T-lymphocytes (PBTL) that have been genetically modified to express the chimeric antigen receptor (CAR) anti-CD19/CD3 zeta chain fusion protein coupled to the intracellular signal domain of CD28 antigen, with potential immunostimulating and antineoplastic activities. Upon administration, autologous PBTL CD19CAR-28 zeta may stimulate host cytotoxic T lymphocyte (CTL) and antibody responses against CD19-expressing tumor cells, resulting in tumor cell lysis. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. CD3 zeta is one of several membrane-bound polypeptides found in the T-cell receptor (TCR)/CD3 complex and regulates the assembly of complete TCR complexes and their expression on the cell surface. CD28 is essential for CD4+ T-cell proliferation, interleukin-2 production, and T-helper type-2 (Th2) development.
  • Autologous pd-1 antibody-expressing mesothelin-specific car-t cells - Genetically modified, autologous T-lymphocytes that express an antibody that targets the negative immunoregulatory human cell surface receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and are transduced with a gene encoding a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) mesothelin, with potential immunomodulating and antineoplastic activities. After isolation, transduction, expansion in culture, and reintroduction into the patient, the autologous PD-1 antibody expressing mesothelin specific CAR-T cells specifically target and kill mesothelin-expressing tumor cells. The anti-PD-1 expressed on the CAR-T cells binds to PD-1 expressed on T-cells and prevents the interaction of PD-1 with its ligand programmed cell death 1 ligand 1 (PD-L1, PD-1L1; CD274) expressed on cancer cells, which prevents PD-1-mediated signaling and T-cell exhaustion, enhances T-cell activation, and results in enhanced toxicity in mesothelin-expressing tumor cells. PD-1, an immunoglobulin (Ig) superfamily transmembrane protein and inhibitory receptor, negatively regulates T-cell activation and overexpression within the tumor microenvironment and inhibits T-cell function. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types.
  • Autologous pd1-inhibiting anti-cd19 4-1bb car t cells - A preparation of autologous T-lymphocytes that are transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19) linked to the intracellular signaling domain of 4-1BB (CD137) that also encodes a cell-intrinsic programmed cell death 1 (PD1; PDCD1; CD279; programmed death-1) short/small hairpin RNA (shRNA)-expressing cassette, with potential immunomodulating and antineoplastic activities. Upon administration of the autologous PD1-inhibiting anti-CD19 4-1BB CAR T-cells, these cells target, bind to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The shRNA silences expression of PD1, abrogates T-cell exhaustion, increases CAR T-cell activity and enhances tumor cytotoxicity. Expression of PD-1, an inhibitory receptor expressed on activated T-cells, plays a key role in CTL suppression, T-cell exhaustion and CTL apoptosis.
  • Autologous pd-1-targeted chimeric switch receptor-modified t lymphocytes - Autologous human T-lymphocytes that are genetically engineered to express a chimeric switch receptor (CSR) composed of the extracellular ligand binding domain of the human inhibitory receptor programmed cell death protein 1 (PD-1; PDCD1) fused to the transmembrane and cytoplasmic co-stimulatory signaling domains of CD28 (PD1CD28; PD-1:CD28 switch receptor), with potential immunomodulating and antineoplastic activities. Upon reintroduction of autologous PD-1-targeted CSR-modified T-lymphocytes into the patient, the switch receptor expressed by the engineered T-cells targets and binds to the PD-1 ligands, programmed cell death ligand 1 (PD-L1) and 2 (PD-L2) expressed, on tumor cells. The nature of the PD-1/CD28 switch receptor fusion protein prevents the normal PD1/PD-L1-mediated T-cell suppression and, instead, promotes signaling through the CD28 domain, which results in the stimulation of T-lymphocytes. This induces enhanced toxicity against PD-L1-expressing tumor cells. PD-1 protein, found on activated T-cells, negatively regulates T-cell activity; it plays a key role in immune evasion and prevents tumor cell lysis. Exchanging the transmembrane and intracellular domain of PD-1 with that of CD28 converts PD-L1 into a co-stimulation ligand of primary human CD8+ cytotoxic T-lymphocytes (CTLs). CD28, is a molecule expressed by T-cells that stimulates increased T-lymphocyte proliferation and activity.
  • Autologous pd-l1/cd80/cd86-targeted car-t cells - A preparation of autologous human T-lymphocytes engineered to express a chimeric antigen receptor (CAR) composed of a modified from of the human inhibitory receptor programmed cell death protein 1 (PD-1; PDCD1), in which the intracellular signal domain of PD-1 is transformed to allow for stimulatory signaling but with an intact extracellular ligand binding domain that specifically binds the tumor-associated antigen (TAA) programmed cell death-1 ligand 1 (PD-L1), and a modified form of the T-cell inhibitory receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with a transformed intracellular signal domain to allow for stimulatory signaling, which specifically binds the B7 proteins CD80 (B7-1) and CD86 (B7-2), with potential immunostimulating and antineoplastic activities. Usually, ligand binding to PD-1 and CTLA-4 inhibits T-cell activity; however, these modified forms of PD-1 and CTLA-4 promote T-cell stimulatory signaling. Upon administration, the autologous PD-L1/CD80/CD86-targeted CAR-T cells target and bind to PD-L1 expressed on certain tumor cells and to CD80/CD86 expressed on antigen-presenting cells (APCs). This stimulates T-cell activation, T-cell proliferation and enhanced cytokine production, which induces selective toxicity in tumor cells expressing PD-L1. PD-1, found on activated T-cells, negatively regulates T-cell activity; it plays a key role in immune evasion and prevents tumor cell lysis. PD-L1 is often overexpressed on tumor cell types and plays a key role in immune evasion. The co-stimulatory molecules CD80 and CD86 play a key role in T-lymphocyte activation upon binding to CD28 upon antigen recognition; however, binding of CD80 and CD86 to wild-type CTLA-4 inhibits T-cell activity and results in T-cell exhaustion.
  • Autologous peripheral blood lymphocytes cotransduced with retroviral vectors encoding inducible il-12 and anti-ny-eso-1 tcr - Human autologous peripheral blood lymphocytes (PBLs) transduced with two retroviral vectors, one encoding a T-cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1 and a second that encodes an inducible single chain form of interleukin-12 (IL-12) driven by a nuclear factor of activated T-cells (NFAT)-responsive promoter, with potential immunomodulating and antineoplastic activities. Following isolation of lymphocytes, retroviral vector transduction, and expansion of the cells ex vivo, the inducible IL-12/anti-NY-ESO-1 TCR-expressing autologous PBLs are re-administered into the patient by intravenous injection. As the transduced PBLs traverse the patient's circulation, they can bind to NY-ESO-1-overexpressing tumor cells. This binding activates the TCR signaling pathway in the transduced PBLs, which promotes NFAT-dependent gene transcription and induces expression of the cotransduced IL-12. IL-12 expression activates the immune system by promoting the secretion of interferon-gamma, activating natural killer cells (NKs), and inducing cytotoxic T-cell responses, which may result in both decreased cell proliferation and increased cell death for the NY-ESO-1-overexpressing tumor cells. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types. NFAT, a family of transcription factors involved in immune responses, is activated by calcium signaling, which can occur downstream of TCR activation. Use of a retroviral vector to express an inducible IL-12 may remove the requirement for concomitant administration of interleukin-2 (IL-2) as is the case for conventional cell transfer immunotherapies.
  • Autologous peripheral blood lymphocytes from ibrutinib-treated chronic lymphocytic leukemia patients iov-2001 - A preparation of autologous peripheral blood lymphocytes (PBLs) harvested from chronic lymphocytic leukemia (CLL) patients previously treated with the Brutons' tyrosine kinase (BTK) inhibitor ibrutinib with potential immunostimulating and antineoplastic activities. Upon intravenous administration, IOV-2001 generates an enhanced cytotoxic T-cell response against autologous leukemic B-cells in patients who have relapsed during treatment with ibrutinib. IOV-2001 is mostly comprised of T-cells of which the majority are of the effector memory phenotype which augments the specificity of the immune response.
  • Autologous prostate cancer antigen-expressing dendritic cell vaccine bpx-101 - A genetically-modified autologous dendritic cell-based vaccine expressing a drug-inducible costimulatory CD40 receptor (iCD40) with potential immunomodulating and antineoplastic activities. Autologous dendritic cells (DCs) are genetically modified to express the iCD40 receptor and are pulsed with the tumor antigen prostate-specific membrane antigen (PSMA). Upon intradermal administration, these DCs accumulate in local draining lymph nodes. Twenty-four hours after vaccination, the dimerizer agent AP1903 is administered; AP1903 binds to and activates iCD40 receptors presented on DC surfaces, thus activating the DCs and stimulating a cytotoxic T-lymphocyte (CTL) response against host tumor cells that express PSMA. This delayed activation strategy optimizes DC accumulation in local draining lymph nodes prior to DC activation. iCD40 contains a membrane-localized cytoplasmic CD40 domain fused to a drug-binding domain.
  • Autologous prostate stem cell antigen-specific car t cells bpx-601 - A preparation of autologous T-lymphocytes expressing a chimeric antigen receptor (CAR) consisting of an anti-human prostate stem cell antigen (PSCA) scFv (single chain variable fragment) coupled to the zeta chain of the T-cell receptor (TCRzeta) and a drug-induced co-stimulatory molecule, composed of an inducible, chimeric MyD88/CD40 (inducible MC; iMC) co-stimulatory domain, in which both the MyD88 and CD40 lack their extracellular domains, with potential antineoplastic activity. Upon administration of BPX-601, the T-cells target and bind to PSCA-expressing cancer cells. Upon subsequent administration of the chemical inducer of dimerization (CID) agent rimiducid, this agent targets and binds to the drug binding domain, which leads to iMC expression, activation of both CD40- and MyD88-mediated signal transduction pathways, and an induction of selective cytotoxicity in, and eradication of PSCA-expressing cancer cells. iMC activation by rimiducid increases T-cell survival and anti-tumor activity of the administered T-cells, compared to T-cells without the drug iMC activation-switch. As these T-cells are engineered to only be fully activated by binding to both antigen and rimiducid, T-cell proliferation, activity and toxicity can be controlled by adjusting the dose of rimiducid, thereby preventing uncontrolled T-cell activation which increases the safety of the administered T-cells. PSCA is a glycosylphosphatidylinositol (GPI)-anchored cell surface antigen overexpressed in many cancer cell types.
  • Autologous psma-4scar-expressing t-cells 4scar-psma - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-prostate-specific membrane antigen (PSMA) single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (CD3zeta; CD3z), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon administration, autologous PSMA-4SCAR-expressing T-cells 4SCAR-PSMA are directed to and induce selective toxicity in PSMA-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.
  • Autologous psma-specific tgfb-resistant car t cells - Autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-prostate specific membrane antigen (PSMA) single chain variable fragment (scFv) and expressing a dominant negative (DN) form of transforming growth factor-beta (TGF-beta; TGFb) receptor, with potential immunomodulating and antineoplastic activities. Upon transfusion, the autologous PSMA-specific TGFb-resistant CAR T cells are directed to and induce selective toxicity in PSMA-expressing tumor cells. The tumor-associated antigen (TAA) PSMA is overexpressed by prostate cancers; its expression is associated with poor prognosis and metastasis. The inclusion of the DN TGFb receptor blocks signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the CAR T cells resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and plays a key role in tumor immune suppression.
  • Autologous rapamycin-resistant th1/tc1 cells rapa-201 - A preparation of autologous rapamycin-resistant Th1/Tc1 cells, with potential immunomodulating activity. Upon administration, autologous rapamycin-resistant Th1/Tc1 cells RAPA-201 may recognize and kill tumor cells. Ex-vivo induction of rapamycin-resistance may increase the persistence of T-cells after adoptive transfer.
  • Autologous renal cell carcinoma tumor lysate-pulsed dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with renal cell carcinoma (RCC) tumor cell lysate containing tumor associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, autologous renal cell carcinoma tumor lysate-dendritic cell vaccine may stimulate anti-tumoral cytotoxic T-lymphocyte (CTL) and antibody responses against RCC tumor cells expressing RCC TAAs, resulting in RCC tumor cell lysis.
  • Autologous ror2-targeted car t-cells cct301-59 - A preparation of genetically modified autologous T-lymphocytes transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) targeting the receptor tyrosine kinase-like orphan receptor 2 (ROR2), with potential immunomodulatory and antineoplastic activities. After isolation, transduction, and expansion in culture, CCT301-59 cells are reintroduced into the patient and are activated within the tumor microenvironment (TME) using proprietary Conditionally Active Biologic (CAB) technology. Upon activation, CAB antibodies bind to a proprietary T-cell signaling domain, promoting T-cell recognition and killing of ROR2-expressing tumor cells. ROR2 is involved in Wnt signal transduction and is involved in tumorigenesis and progression. ROR2 expression is upregulated in certain tumor types and high levels of ROR2 expression often correlates with poor prognosis.
  • Autologous sarcoma cell lysate - A cell lysate derived from sarcoma cells with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the autologous sarcoma cell lysate exposes the immune system to an undefined amount of sarcoma-type tumor associated antigens (TAA), which may result in the induction of both specific anti-tumoral cytotoxic T lymphocytes (CTL) and antibody-dependent responses against the sarcoma TAA-expressing cells, resulting in sarcoma cell lysis.
  • Autologous sarcoma lysate-pulsed dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysates from sarcoma cells with potential immunostimulatory and antineoplastic activities. Upon administration, the autologous sarcoma lysate-pulsed dendritic cell vaccine exposes the immune system to an undefined amount of sarcoma-type tumor associated antigens (TAA), which may result in the induction of both specific anti-tumoral cytotoxic T lymphocytes (CTL) and antibody-dependent responses against the sarcoma TAA-expressing cells, resulting in sarcoma cell lysis.
  • Autologous taas-loaded autologous dendritic cells av-gbm-1 - A preparation of autologous dendritic cells (DCs) loaded with immunogenic tumor-associated antigens (TAAs) derived from cultured autologous glioblastoma multiforme (GBM) tumor cells, with potential immunostimulatory and antineoplastic activities. Upon administration, the autologous TAA-loaded DCs AV-GBM-1 expose the immune system to the GBM neoantigens, which results in a cytotoxic T-lymphocyte (CTL)-mediated immune response against the autologous GBM cells leading to GBM cell lysis.
  • Autologous tcr-engineered t-cells ima201 - A preparation of autologous T-lymphocytes that are genetically modified with a lentiviral vector encoding a T-cell receptor (TCR) specific for an as of yet not identified tumor-associated antigen (TAA), with potential antineoplastic activity. Upon intravenous administration back into the patient, the autologous TCR-engineered T-cells IMA201 specifically recognize and bind to the TAA on cancer cells, which induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against the TAA-positive cancer cells.
  • Autologous tcr-engineered t-cells ima202 - A preparation of autologous T-lymphocytes that are genetically modified with a lentiviral vector encoding a T-cell receptor (TCR) targeting patient-specific tumor associated antigens (TAAs), with potential antineoplastic activity. Upon intravenous administration back into the patient, the autologous TCR-engineered T-cells IMA202 specifically recognize and bind to the TAA on cancer cells, which induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against the TAA-positive cancer cells.
  • Autologous tcr-engineered t-cells ima203 - A preparation of autologous T-lymphocytes that are genetically modified with a viral vector encoding a T-cell receptor (TCR) targeting an as of yet undisclosed patient-specific tumor associated antigen (TAA), with potential antineoplastic activity. Upon intravenous administration back into the patient, the autologous TCR-engineered T-cells IMA203 specifically recognize and bind to the TAA on cancer cells, which induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against the TAA-positive cancer cells.
  • Autologous tcrm-expressing t-cells et140203 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector to express a T-cell receptor mimetic (TCRm) construct targeting as of yet undisclosed tumor associated antigen(s) (TAA), with potential immunomodulatory and antineoplastic activities. Upon administration, the autologous TCRm-expressing T-cells ET140203 specifically recognize and selectively bind to the as of yet undisclosed TAA(s). This results in cytotoxic T-lymphocyte (CTL)-mediated killing of tumor cells expressing the TAA(s).
  • Autologous tetravalent dendritic cell vaccine midrix4-lung - A therapeutic cancer vaccine composed of autologous, dendritic cells (DCs) that have been loaded with a proprietary selection of four antigens that covers more than ninety percent of all non-small cell lung cancer (NSCLC) patients, with potential immunostimulatory and antineoplastic activities. Upon administration, autologous tetravalent dendritic cell vaccine MIDRIX4-LUNG may induce and stimulate both T-helper and antigen-specific cytotoxic T-lymphocyte (CTL) responses, leading to tumor cell lysis in patients with NSCLC.
  • Autologous tgfbeta-resistant her2/ebv-specific cytotoxic t lymphocytes - A preparation of transforming growth factor-beta (TGF-beta)-resistant Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs) directed to EBV through their native receptor and HER2 through a retrovirally transduced HER2 chimeric antigen receptor (CAR) with potential antineoplastic activity. Autologous EBV-specific CTLs are produced by exposing autologous CTLs to "stimulator" autologous EBV-transformed lymphoblastoid cell lines (EBV-LCLs). Subsequently, autologous EBV-specific CTLs are transduced with retroviral vectors expressing the mutant type II TGF-beta dominant-negative receptor (DNR), which blocks signaling by all three TGF-beta isoforms, and the HER2 CAR. After transduction, transgenic EBV-CTLs are expanded on EBV-LCLs. Upon administration, autologous HER2 chimeric receptor/TGFbeta dominant negative receptor-expressing EBV-specific cytotoxic T lymphocytes may bind to HER2-expressing tumors cells, which may result in CTL-mediated cell lysis and inhibition of tumor cell proliferation. Tumor-expressed TGF-beta inhibits T lymphocyte activation and expansion.
  • Autologous t-lymphocytes-expressing ny-eso-1-c259-specific enhanced t-cell receptors - Human autologous lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the cancer/testis antigen NY-ESO-1, with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the autologous T-lymphocytes expressing NY-ESO-1-C259-specific enhanced T-cell receptors bind to NY-ESO-1-overexpressing tumor cells. This may result in the specific cytotoxic T-lymphocyte (CTL) killing of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types; the TCR is specific for SLLMWITQC, an NY-ESO-1-derived peptide, in a complex with human leukocyte antigen (HLA) A2 peptide.
  • Autologous tn-muc1-specific car t-lymphocytes - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) Tn glycoform of mucin-1 (Tn-MUC1; TnMUC1), with potential antineoplastic and immunostimulating activities. Upon re-introduction into the patient, the autologous Tn-MUC1-specific CAR T-lymphocytes specifically recognize and induce selective toxicity in TnMUC1-expressing tumor cells. TnMUC1 is overexpressed in certain tumor types.
  • Autologous tumor cell proteoliposome chronic lymphocytic leukemia vaccine - An autologous chronic lymphocytic leukemia cancer vaccine consisting of patient-specific membrane proteins directly extracted from patient autologous tumor cells and incorporated into liposomes along with Interleukin 2 (IL-2) to produce membrane-patched proteoliposomes, with potential immunostimulating and antineoplastic activities. After subcutaneous injection of the autologous tumor cell proteoliposomes chronic lymphocytic leukemia vaccine, liposomes deliver the encapsulated tumor antigens into the cytosol of antigen presenting cells (APCs). Subsequently, the APCs process the antigens and present antigen-derived peptides to the immune system. This may enhance recognition of tumors by the immune system, and activate both cytotoxic CD8+ T cells and CD4+ helper T cells against tumor cells. IL-2 is incorporated into the vaccine to leverage its ability to expand activated T cells.
  • Autologous tumor cell vaccine - A therapeutic agent produced by isolating tumor cells from an individual and processing these tumor cells into a vaccine formulation in vitro; the vaccine is then administered to the individual from whom the tumor cells were isolated. Typically combined with an adjuvant immunostimulant, an autologous cell vaccine may elicit a cytotoxic T-lymphocytic immune response to cell surface-expressed tumor-associated antigens (TAAs), resulting in tumor cell death.
  • Autologous tumor infiltrating lymphocytes ln-145 - A proprietary preparation of autologous tumor infiltrating lymphocytes (TILs), with potential immunomodulating activity. The autologous TILs are isolated from an autologous tumor sample and expanded ex vivo in the presence of interleukin-2 (IL-2). Upon infusion of the autologous TILs LN-145 back into the patient, the cells specifically recognize, target and kill the patient's tumor cells.
  • Autologous tumor infiltrating lymphocytes ln-145-s1 - A proprietary preparation of autologous tumor infiltrating lymphocytes (TILs), with potential immunomodulating and antineoplastic activities. The autologous TILs are isolated from an autologous tumor sample and expanded ex vivo in the presence of interleukin-2 (IL-2). Upon infusion of the autologous TILs LN-145-S1 back into the patient, the cells specifically recognize, target and kill the patient's tumor cells.
  • Autologous tumor infiltrating lymphocytes mda-til - A preparation of autologous tumor infiltrating lymphocytes (TILs) with potential antineoplastic activity. TILs are isolated from a patient's tumor tissue, then cultured and expanded in vitro in the presence of interleukin-2 (IL-2) and an agonistic anti-4-1BB (CD137) antibody. Upon infusion of the autologous expanded TILs back into the patient, the cells specifically recognize, target, and kill the patient's tumor cells.
  • Autologous tumor-associated peptide antigen-pulsed dendritic cell vaccine - A dendritic cell (DC)-based cancer vaccine composed of autologous DCs pulsed with specific tumor-associated peptide antigens (TAPA), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous TAPA-pulsed DC vaccine exposes the immune system to the specific TAPAs, which may result in cytotoxic T-lymphocyte (CTL)-mediated immune responses against the TAPA-expressing cancer cells. This leads to cancer cell lysis. This vaccine is specific towards peptides derived from the following proteins: sperm autoantigenic protein 17 (SP17), ropporin, A-kinase anchor protein 4 (AKAP4), pituitary tumor-transforming 1 (PTTG1) and SPANX family member B (SPANX-B).
  • Autologous tumor-specific antigen-loaded dendritic cells - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) loaded with tumor-specific antigen(s) (TSAs), with potential immunostimulatory and antineoplastic activities. Upon administration of the autologous TSA-loaded DCs, the DCs stimulate a specific cytotoxic T-lymphocyte (CTL)-mediated immune response against the tumor cells expressing the TSA(s), resulting in tumor cell lysis.
  • Autologous ucd19 car t cells - A preparation of autologous peripheral blood lymphocytes (PBLs) that have been transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon transfusion, the autologous UCD19 CAR T-cells recognize and bind to CD19-expressing tumor cells, thereby selectively lysing CD19-expressing tumor cells. CD19, a B-cell-specific cell surface antigen is overexpressed in B-cell lineage malignancies.
  • Autologous universal car-expressing t-lymphocytes unicar02-t - A preparation of autologous T-lymphocytes that has been genetically engineered to express a fully humanized, universal, second generation chimeric antigen receptor (CAR) with a CD28/CD3zeta co-stimulatory domain, and a binding domain that can recognize a peptide motive of an antigen-specific targeting module (TM), with potential immunomodulating and antineoplastic activities. Upon administration, autologous universal CAR-expressing T-lymphocytes UniCAR02-T remain inactivated. Upon administration of an antigen-specific TM, the binding domain of UniCAR02-T binds to the nuclear antigen motif of the TM, and UniCAR02-T is activated when the antigen-binding moiety of the TM binds to the specific antigen expressed on tumor cells. This induces selective toxicity in and causes lysis of tumor cells expressing the specific antigen.
  • Autologous wt1-tcrc4 gene-transduced cd8-positive tcm/tn lymphocytes - Autologous, human CD8 T-lymphocytes, comprised of both central memory T-cells (Tcm) and na├»ve T-cells (Tn), that are transduced, ex vivo, with a self-inactivating (SIN) lentiviral vector encoding a high-affinity T-cell receptor (TCRc4) specific for the human tumor antigen Wilms tumor 1 (WT1) epitope 126-134 (RMFPNAPYL), with potential antineoplastic activity. Upon isolation of peripheral blood lymphocytes (PBLs), transduction, expansion ex vivo, priming of the Tn subset, but not the Tcm subset, with interleukin-21 (IL-21) and reintroduction of equal amounts of Tcm and Tn cells into the patient, WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes redirect T-lymphocytes to WT1-expressing tumor cells and specifically bind to and lyse those cells. This inhibits proliferation of WT1-expressing tumor cells. WT1 protein, a zinc finger DNA-binding transcriptional regulator, is overexpressed in most leukemias and various solid tumors, while expression in normal, healthy tissues is very limited; its expression is correlated with aggressiveness and poor prognosis.
  • Avadomide - A novel, small molecule cereblon-modulating agent with potential antineoplastic, antiangiogenic and immunomodulatory activities. Upon oral administration, avadomide binds to and modulates cereblon to promote recruitment of the hematopoietic transcription factors Aiolos and Ikaros to the Cullin-4 RING E3 ubiquitin ligase complex. This binding results in the ubiquitination and rapid proteasomal degradation of Aiolos and Ikaros and the derepression of interferon (IFN)-stimulated genes, including DDX58 and IRF7, leading to apoptosis of certain tumor cells. Additionally, Aiolos degredation leads to derepression of the IL2 gene, thereby enhancing interleukin-2 production, costimulation of T-lymphocytes and IL-2-induced T-cell proliferation. Avadomide may also promote the activation of natural killer (NK) cells, potentially enhancing tumor cell killing. Aiolos and Ikaros are transcriptional repressors known to play an important role in normal B- and T-cell function.
  • Avadomide hydrochloride - The hydrochloride salt form of avadomide, a novel, small molecule, cereblon-modulating agent with potential antineoplastic, antiangiogenic and immunomodulatory activities. Upon oral administration, avadomide binds to and modulates cereblon to promote recruitment of the hematopoietic transcription factors Aiolos and Ikaros to the Cullin-4 RING E3 ubiquitin ligase complex. This binding results in the ubiquitination and rapid proteasomal degradation of Aiolos and Ikaros and the derepression of interferon (IFN)-stimulated genes, including DDX58 and IRF7, leading to apoptosis of certain tumor cells. Additionally, Aiolos degredation leads to derepression of the IL2 gene, thereby enhancing interleukin-2 production, costimulation of T-lymphocytes and IL-2-induced T-cell proliferation. Avadomide may also promote the activation of natural killer (NK) cells, potentially enhancing tumor cell killing. Aiolos and Ikaros are transcriptional repressors known to play an important role in normal B- and T-cell function.
  • Avapritinib - An orally bioavailable inhibitor of specific mutated forms of platelet-derived growth factor receptor alpha (PDGFR alpha; PDGFRa) and mast/stem cell factor receptor c-Kit (SCFR), with potential antineoplastic activity. Upon oral administration, avapritinib specifically binds to and inhibits specific mutant forms of PDGFRa and c-Kit, including the PDGFRa D842V mutant and various KIT exon 17 mutants. This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants. PDGFRa and c-Kit, protein tyrosine kinases and tumor-associated antigens (TAAs), are mutated in various tumor cell types; they play key roles in the regulation of cellular proliferation.
  • Avdoralimab - A human monoclonal antibody targeting the C5a receptor (C5aR), with potential immunomodulating activity. Upon administration, avdoralimab specifically targets, binds to and blocks C5aR expressed on subsets of myeloid-derived suppressor cells (MDSCs) and neutrophils. This prevents the binding of its ligand C5a to C5aR and prevents the C5aR-mediated activation and accumulation of these cells in the tumor microenvironment (TME), and abrogates the secretion of inflammatory and angiogenic factors by these cells. This results in the activation of T- and natural killer (NK) cells, the induction of anti-tumor immune responses and inhibits tumor cell proliferation. C5a, a factor in the complement cascade, is often overexpressed in tumors, where it attracts and activates MDSCs and neutrophils in the TME.
  • Avelumab - A human immunoglobulin G1 (IgG1) monoclonal antibody directed against the human immunosuppressive ligand programmed death-ligand 1 (PD-L1) protein, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, avelumab binds to PD-L1 and prevents the interaction of PD-L1 with its receptor programmed cell death protein 1 (PD-1). This inhibits the activation of PD-1 and its downstream signaling pathways. This may restore immune function through the activation of cytotoxic T-lymphocytes (CTLs) targeted to PD-L1-overexpressing tumor cells. In addition, avelumab induces an antibody-dependent cellular cytotoxic (ADCC) response against PD-L1-expressing tumor cells. PD-1, a cell surface receptor belonging to the immunoglobulin superfamily expressed on T-cells, negatively regulates T-cell activation and effector function when activated by its ligand, and plays an important role in tumor evasion from host immunity. PD-L1, a transmembrane protein, is overexpressed on a variety of tumor cell types and is associated with poor prognosis.
  • Aviscumine - A recombinant protein that inactivates the ribosome with potential antineoplastic and immunomodulating activities. Aviscumine binds to the cell surface sialyltransferase CD75 and is internalized; intracellularly, aviscumine cleaves an adenine-specific N-glycosidic bond on the 28S ribosomal subunit, which may result in tumor cell apoptosis. This agent has also been shown to activate natural killer (NK) cells, induce cytokine receptor expression, and stimulate the release of cytokines. CD75 is expressed on mature B-cells and subsets of T-cells and erythrocytes.
  • Avitinib maleate - The maleate salt form of avitinib, an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, avitinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of cancers, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR.
  • Axalimogene filolisbac - A cancer vaccine containing a live-attenuated strain of the bacterium Listeria monocytogenes (Lm) encoding human papillomavirus (HPV) type 16 E7 fused to a non-hemolytic listeriolysin O protein with potential immunostimulatory and antineoplastic activities. Upon vaccination with axalimogene filolisbac, Listeria expresses the HPV 16 E7 antigen and activates the immune system to mount a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing HPV 16 E7. This may result in tumor cell lysis. In addition, the Listeria vector itself may induce a potent immune response. HPV 16 E7, a cell surface glycoprotein and tumor associated antigen, is overexpressed in the majority of cervical cancer cells.
  • Axatilimab - A humanized immunoglobulin (Ig) G4 monoclonal antibody directed against colony-stimulating factor 1 receptor (CSF-1R), with potential antineoplastic activity. Upon intravenous administration, axatilimab binds to the ligand binding domain of CSF-1R, preventing binding and consequent activation by its natural ligands, IL-34 and colony-stimulating factor 1 (CSF-1). Inhibition of CSF-1R activation may disrupt the activity of tumor-associated macrophages (TAMs), which promote initiation and metastasis of tumor cells, inhibit T-cell responses, and stimulate tumor angiogenesis and disease progression. CSF-1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and cluster of differentiation 115 (CD115), is a tyrosine-protein kinase that plays an essential role in the regulation, proliferation, survival and differentiation of tissue macrophages as well as TAMs.
  • Axicabtagene ciloleucel - A preparation of autologous peripheral blood T-lymphocytes (PBTL) that have been transduced with a gammaretoviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv) coupled to the costimulatory signaling domain CD28 and the zeta chain of the T-cell receptor (TCR)/CD3 complex (CD3 zeta), with potential immunostimulating and antineoplastic activities. Upon intravenous infusion and re-introduction of axicabtagene ciloleucel into the patient, these cells bind to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen that is expressed in all B-cell lineage malignancies. CD3 zeta is one of several membrane-bound polypeptides found in the TCR/CD3 complex; it regulates both the assembly and cell surface expression of TCR complexes. CD28 is essential for CD4+ T-cell proliferation, interleukin-2 production, and T-helper type-2 (Th2) development.
  • Axitinib - An orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect.
  • Axl inhibitor ds-1205c - An orally available and selective inhibitor of the receptor tyrosine kinase AXL (UFO), with potential antineoplastic activity. Upon administration, DS-1205c targets, binds to and prevents the activation of AXL. This blocks AXL-mediated signal transduction pathways and inhibits tumor cell proliferation and migration. AXL, a member of the Tyro3, AXL and Mer (TAM) family of receptor tyrosine kinases, is overexpressed by many tumor cell types. It plays a key role in tumor cell proliferation, survival, invasion and metastasis; its expression is associated with drug resistance and poor prognosis.
  • Axl inhibitor slc-391 - An orally bioavailable and selective inhibitor of the receptor tyrosine kinase AXL (UFO), with potential immunostimulating and antineoplastic activities. Upon oral administration, SLC-391 targets, binds to and prevents the activation of AXL. This blocks AXL-mediated signal transduction pathways, and inhibits both AXL-mediated tumor cell growth, proliferation and migration and AXL-mediated immunosuppression. AXL, a member of the Tyro3, AXL and Mer (TAM) family of receptor tyrosine kinases, is overexpressed by many tumor cell types and also expressed in a variety of immune cells including macrophages, natural killer (NK) cells, and regulatory T-cells (Tregs). It plays a key role in tumor cell proliferation, survival, invasion and metastasis, and is a mediator of immunosuppression. Its expression is associated with drug resistance and poor prognosis.
  • Axl receptor tyrosine kinase/cmet inhibitor bpi-9016m - An orally available inhibitor of the AXL receptor tyrosine kinase (AXL; UFO) and the receptor tyrosine kinase c-Met/hepatocyte growth factor receptor (HGFR) with antineoplastic activity. Upon administration, AXL receptor tyrosine kinase/cMET inhibitor BPI-9016M, binds to both AXL and cMet, thereby disrupting both AXL- and c-Met-mediated signaling pathways. Altogether, this agent inhibits growth in AXL and cMet-overexpressing tumor cells. AXL, a member of the TAM (TYRO3, AXL and MER) family of receptor tyrosine kinases, and cMet, both overexpressed by many tumor cell types, play key roles in tumor cell proliferation, survival, invasion and metastasis.
  • Axl/ flt3/vegfr2 inhibitor kc1036 - An orally bioavailable inhibitor of three receptor tyrosine kinases: AXL (UFO), FMS-like tyrosine kinase-3 (Flt3; CD135; fetal liver kinase-2; Flk2), and the vascular endothelial growth factor receptor type 2 (VEGFR2), with potential anti-angiogenesis and antineoplastic activities. Upon oral administration, KC1036 targets, binds to and prevents the activation of AXL, FLT3 and VEGFR2. This blocks AXL, FLT3 and VEGFR2-mediated signal transduction pathways, and inhibits both AXL-, FLT3- and VEGFR2-mediated proliferation of tumor cells and the VEGFR2-mediated proliferation, survival and migration of endothelial cells. AXL, a member of the Tyro3, AXL and Mer (TAM) family of receptor tyrosine kinases, is overexpressed by many tumor cell types and also expressed in a variety of immune cells including macrophages, natural killer (NK) cells, and regulatory T-cells (Tregs). It plays a key role in tumor cell proliferation, survival, invasion and metastasis, and is a mediator of immunosuppression. Its expression is associated with drug resistance and poor prognosis. FLT3, a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage and acute myeloid leukemias. VEGFR2 is frequently overexpressed by a variety of tumor types and tumor-associated endothelial cells.
  • Axl/mer inhibitor incb081776 - An orally available and selective inhibitor of the receptor tyrosine kinases (RTKs) Axl (UFO) and Mer, with potential antineoplastic activity. Upon administration, INCB081776 targets and binds to both Axl and Mer, and prevents their activity. This blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells. Axl and Mer, both members of the TAM (Tyro3, Axl and Mer) family of RTKs, are overexpressed by many tumor cell types. They play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and their expression is associated with enhanced immunosuppression, drug resistance and poor prognosis.
  • Axl/mer inhibitor pf-07265807 - An inhibitor of the receptor tyrosine kinases (RTKs) Axl (UFO) and Mer, with potential antineoplastic activity. Upon administration, Axl/Mer inhibitor PF-07265807 specifically targets and binds to both Axl and Mer, and prevents their activity. This blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells. Axl and Mer, both members of the TAM (Tyro3, Axl and Mer) family of RTKs, are overexpressed by many tumor cell types. They play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and their expression is associated with drug resistance and poor prognosis.
  • Azacitidine - A pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Azacitidine is incorporated into DNA, where it reversibly inhibits DNA methyltransferase, thereby blocking DNA methylation. Hypomethylation of DNA by azacitidine may activate tumor suppressor genes silenced by hypermethylation, resulting in an antitumor effect. This agent is also incorporated into RNA, thereby disrupting normal RNA function and impairing tRNA cytosine-5-methyltransferase activity.
  • Azapicyl - A hydrazine compound that has been investigated for antineoplastic activity.
  • Azaribine - The triacetate salt of azauridine, a synthetic triazine nucleoside derivative possessing antineoplastic and anti-psoriatic activity. After metabolism to 6-azauridine-5-prime monophosphate, 6-Azauridine inhibits de novo pyrimidine biosynthesis and its 5-prime triphosphate metabolite gets incorporated into RNA, thereby preventing RNA synthesis.
  • Azaserine - A naturally occurring serine derivative diazo compound with antineoplastic properties, Azaserine functions as a purine antagonist and glutamine analogue (glutamine amidotransferase inhibitor) that competitively inhibits pathways in which glutamine is metabolized. An antibiotic and antitumor agent, Azaserine is used in clinical studies as a potential antineoplastic agent.
  • Azimexon - Azimexon (2-cyanaziridinyl-2-carbamoyl-aziridinyl-1-propane) is a derivative of 2-cyanaziridine. Immunostimulant which shows therapeutic effects in tumor models and experimental infections in vitro, enhancing T lymphocyte transformation and phagocytosis. The mode of action of azimexon is unknown. It has been suggested that azimexon may alkylate DNA. In cancer patients it increases leukocytosis, blood active T rosettes, T4/T8 ratio, and is used as an adjuvant to chemotherapy in the treatment of melanoma and myeloma.
  • Azintuxizumab vedotin - An antibody-drug conjugate (ADC) composed of an antibody targeting CS1 (SLAMF7/CD319) that is conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), via a cathepsin-cleavable linker, with potential antineoplastic activity. Upon administration, the antibody moiety of azintuxizumab vedotin binds to CS1-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Upon cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M checkpoint arrest and apoptosis in CS1-expressing tumor cells. CS1 is a cell surface glycoprotein belonging to the CD2 subset of the immunoglobulin superfamily (IgSF) and is expressed with high levels and prevalence on multiple myeloma (MM) cells.
  • Aziridinylbenzoquinone rh1 - A water-soluble, synthetic aziridinylbenzoquinone with potential antineoplastic activity. Bioactivation of aziridinylbenzoquinone RH1 occurs through the two-electron reduction of the quinone to the hydroquinone by the two-electron quinone reductase DT-diaphorase (DTD). The resultant hydroquinone selectively alkylates and cross-links DNA at the 5'-GNC-3' sequence, inihibiting DNA replication, inducing apoptosis, and inhibiting tumor cell proliferation. DTD is over-expressed in many tumors relative to normal tissue, including lung, colon, breast and liver tumors.
  • Azotomycin - An antineoplastic-antibiotic diazo analog of L-glutamine isolated from the bacterium Streptomyces ambofaciens. Azotomycin inhibits glutamine-dependent enzymes involved in purine and pyrimidine biosynthesis, resulting in inhibition of DNA synthesis.
  • Azurin:50-77 cell penetrating peptide p28 - A water-soluble, amphipathic, 28 amino acid (amino acids 50-77), 2.9 kD fragment peptide (p28) derived from the protein azurin with potential antineoplastic and antiangiogenic activities. Although the mechanism has yet to be fully elucidated, the preferential cellular uptake of azurin-derived cell-penetrating peptide p28 by tumor cells and endothelial cells is likely via caveolae-mediated endocytosis; the C-terminal 18 amino acid residues (50-67) appear to be responsible for this preferential uptake. After cell entry, the first 12 amino acid residues interact with tumor suppressor p53 and form a p28:p53 complex, which may result in a reduction of proteasomal degradation of p53, increased p53 levels, and p53-mediated cell cycle inhibition and apoptosis. Azurin is a cupredoxin secreted by the bacterium Pseudomonas aeruginosa. Cell penetrating peptides (CPPs) are cationic and/or amphipathic peptides, typically less than 30 amino acids in length, that can penetrate cell membranes easily and may transport molecular cargo.

Alphabetic list of antineoplastic agents - 0-9 - A1 - A2 - A3 - A4 - A5 -A6 - B - C - D - E - F - G - H - I - JK - L - M - NO - PQ - R - S - T - UVW - XYZ

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