DENDRITIC CELLS GENETICALLY-MODIFIED WITH AN ADENOVIRUS VECTOR ENCODING THE CDNA FOR A MODEL ANTIGEN INDUCE PROTECTIVE AND THERAPEUTIC ANTITUMOR IMMUNITY

Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in the initiation of antitumor immune responses. In this study, we show that genetic modifications of a murine epidermis-deriv ed DC line and primary bone marrow-derived DCs to express a model anti gen beta-galactosidase (beta gal) can be achieved through the use of a replication-deficient, recombinant adenovirus vector, and that the mo dified DCs are capable of eliciting antigen-specific, MHC-restricted C TL responses. Importantly, using a murine metastatic lung tumor model with syngeneic colon carcinoma cells expressing beta gal, we show that immunization of mice with the genetically modified DC line or bone ma rrow DCs confers potent protection against a lethal tumor challenge, a s well as suppression of preestablished tumors, resulting in a signifi cant survival advantage. We conclude that genetic modification of DCs to express antigens that are also expressed in tumors can lead to anti gen-specific, antitumor killer cells, with a concomitant resistance to tumor challenge and a decrease in the size of existing tumors.