Immunity to breast cancer in mice immunized with X-irradiated breast cancer cells modified to secrete IL-12

A mouse mammary adenocarcinoma cell line (410.4) originating in a BALB/c mo use, was transduced with a retroviral vector (TGF-mIL-12-Neo) that encoded murine IL-12. After confirmation of IL-12-secretion, the cells were tested for their tumorigenic properties in BALB/c mice. The results indicated that unlike other tumors modified for cytokine secretion, modification of 410.4 cells to secrete IL-12 (410.4-IL-12 cells) failed to eliminate the cells' neoplastic growth properties. Progressively growing tumors of 410.4-IL-12 c ells invariably formed in syngeneic BALB/c mice and led, eventually, to the animals' death. However, the cells' immunogenic properties were preserved as indicated by the finding that immunizations with 410.4-IL-12 cells, inac tivated before injection by X-irradiation, resulted in potent, long-term im munity toward unmodified 410.4 cells and protected the mice against the mal ignant proliferation of the breast cancer cells. We conclude that modificat ion of 410.4 cells for IL-12-secretion augmented the response of syngeneic BALB/c mice to weakly immunogenic tumor-associated antigens expressed by th e cells. The increase in the cells' immunogenic properties, however, was in sufficient to prevent tumor growth in the mice. The results point toward th e immunotherapeutic potential of X-irradiated tumor cells modified for the secretion of immune augmenting cytokines.