Efficient co-transduction of adenoviral vectors encoding carcinoembryonic antigen and survivin into dendritic cells by the CAR-TAT adaptor molecule enhance anti-tumor immunity in a murine colorectal cancer model.

摘要

Because multiple tumor antigens, including carcinoembryonic antigen (CEA) and survivin (SVV), have been frequently observed in human colorectal cancer, we investigated whether the expression of both CEA and SVV by co-transduction of adenovirus vectors into dendritic cells (DCs) could improve anti-tumor immunity in a murine colorectal cancer model. The adaptor fusion protein of Coxsackie and adenovirus receptor and TAT-protein transduction domain (CAR-TAT) enhanced co-transduction of adenovirus vectors encoding CEA (AdCEA) and SVV (AdSVV) into DCs, and increased anti-tumor immunity. DCs expressing both CEA and SVV in the presence of CAR-TAT (DC-AdCEA/AdSVV+CAR-TAT) induced T-cell responses specific for CEA and SVV, and enhanced cytotoxic T-cell activity on MC38/CEA2 cells expressing CEA and SVV compared with DCs expressing either CEA or SVV alone. Particularly, DC-AdCEA/AdSVV+CAR-TAT induced higher number of CEA-specific IFN-gamma secreting T cells compared with DC-AdCEA+CAR-TAT. Vaccination with DC-AdCEA/AdSVV+CAR-TAT also more efficiently inhibited tumor growth compared with DCs expressing either CEA or SVV alone in therapeutic tumor models. These results suggest that efficient co-transduction of multiple adenovirus vectors by CAR-TAT could be used to develop various strategies for therapeutic DC vaccines.