Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens

Dendritic cells (DCs) are professional Ag-presenting cells that are being c onsidered as potential immunotherapeutic agents to promote host immune resp onses against tumor Ags, In this study, recombinant adenovirus (Ad) vectors encoding melanoma-associated Ags were used to transduce murine DCs, which were then tested for their ability to activate CTL and induce protective im munity against B16 melanoma tumor cells. Immunization of C57BL/6 mice with DCs transduced with Ad vector encoding the hugp100 melanoma Ag (Ad2/hugp100 ) elicited the development of gp100-specific CTLs capable of lysing syngene ic fibroblasts transduced with Ad2/hugp100, as well as B16 cells expressing endogenous murine gp100, The induction of gp100-specific CTLs was associat ed with long term protection against lethal s.c. challenge with B16 cells. It was also possible to induce effective immunity against a murine melanoma self Ag, tyrosinase-related protein-2, using DCs transduced with Ad vector encoding the Ag, The level of antitumor protection achieved was dependent on the dose of DCs and required CD4(+) T cell activity. Importantly, immuni zation with Ad vector-transduced DCs was not impaired in mice that had been preimmunized against Ad to mimic the immune status of the general human po pulation. Finally, DC-based immunization also afforded partial protection a gainst established B16 tumor cells, and the inhibition of tumor growth was improved by simultaneous immunization against two melanoma-associated Ags a s opposed to either one alone. Taken together, these results support the co ncept of cancer immunotherapy using DCs transduced with Ad vectors encoding tumor-associated Ags.