Tumor gene therapy by MVA-mediated expression of T-cell–stimulating antibodies

摘要: Immune responses to tumor-associated antigens are often dampened by a tumor-induced state of immune anergy. Previous work has attempted overcome T-cell anergy the direct injection vectors carrying genes encoding one variety cytokines. We hypothesised that polyclonal stimulation T cells, preferably through TCR complex, would result in cascade cytokines associated with activation and be best able Here we use highly attenuated MVA poxvirus express on tumor vitro vivo, either three membrane-bound monoclonal antibodies specific for murine complex. Using this system, have expressed CD3ɛ chain (KT3), TCRα/β complex (H57-597), Vβ7 (TR310). Tumor cells bristling these capable inducing proliferation cytokine production. When injected into growing tumors (P815, RenCa, B16F10), constructs induce effector rejection tumor. Histological FACS analysis tumor-infiltrating leukocytes reveal recombinant virus-expressing attracts activates (CD25+, CD69+) CD4 CD8 lymphocytes. This approach represents novel strategy allow tumor-specific cells.