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Adenovirus 5/f35-human guanylyl cyclase c-padre

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A recombinant adenoviral serotype 5 (Ad5) in which the Ad5-based vector fiber is replaced by the fiber from the human B adenovirus serotype 35 (F35), encoding for the human guanylyl cyclase C (hGCC), and fused to the synthetic Pan DR epitope (PADRE), with potential antineoplastic and immunomodulating activities. Upon intramuscular administration of the Ad5/F35-hGCC-PADRE, the Ad5/F35 targets CD46, which is expressed widely on most tumor cells, and the virus is taken up by cells. Once inside the cells, the virus expresses hGCC. The expressed hGCC induces both humoral and cellular immune responses against tumor cells expressing the hGCC antigen. This results in the immune-mediated killing of tumor cells. The hGCC protein is normally restricted to intestinal epithelial cells but is overexpressed by metastatic colorectal tumors. PADRE is a helper T-lymphocyte epitope that is able to augment the magnitude and duration of the cytotoxic T-lymphocyte (CTL) response. The inclusion of the chimeric Ad5/F35 fiber increases viral uptake in cells through CD46.

 

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