AUGMENTATION OF THERAPEUTIC ANTITUMOR IMMUNITY BY B16F10 MELANOMA-CELLS TRANSFECTED WITH INTERFERON-GAMMA AND ALLOGENEIC MHC CLASS-I CDNAS

The cDNAs for interferon-gamma (IFN-gamma) and allogeneic H-2K(d) mole cules were transfected into highly metastatic B16F10 melanoma cells (H -2(b)), and the synergistic effects of the antitumor immune responses by the doubly transfected cells (B16/K-d/IFN-gamma cells) were investi gated in C57BL/6 mice (H-2(b)), The singly transfected B16F10 cells wi th either IFN-gamma or H-2K(d) cDNA (B16/IFN-gamma or B16/K-d cells) w ere used as controls. The B16/K-d/IFN-gamma cells secreted biologicall y active IFN-gamma, and strongly expressed both syngeneic and allogene ic MHC class I antigens (H-2K(b) and H-2K(d)) on the same cell constru ct. Immunization with the doubly transfected B16/K-d/IFN-gamma cells i nduced higher anti B16F10 cellular cytotoxic responses than the single transfected B16/IFN-gamma or B16/K-d cells. Lyt-2.2 (CD8)(+) T-cells were a major effector cell-type involved in the anti B16F10 responses and their cytotoxic activities were augmented in the immunized mice wi th the B16/K-d/IFN-gamma cells, as demonstrated by in vitro depletion experiments. The survival period of melanoma-bearing mice treated with the B16/K-d/IFN-gamma cells was significantly longer than that treate d with the B16/IFN-gamma or B16/K-d cells, Furthermore, the treatment with the B16/K-d/IFN-gamma cells was capable of greatly inhibiting lun g metastasis from small, established B16F10 footpad tumors. These resu lts suggest that the augmented immunotherapeutic potentials can be ach ieved by the vaccination with IFN-gamma and allogeneic MHC class I gen es transfected B16F10 melanoma cells.