Augmentation of Therapeutic Antitumor Immunity by B16F10 Melanoma Cells Transfected with Interferon-γ and Allogeneic MHC Class I cDNAs

Abstract

he cDNAs for interferon-γ (IFN-γ) and allogeneic H-2Kd molecules were transfected into highly metastatic B16F10 melanoma cells (H-2b), and the synergistic effects of the antitumor immune responses by the doubly transfected cells (B16/Kd/IFN-γ cells) were investigated in C57BL/6 mice (H-2b). The singly transfected B16F10 cells with either IFN-γ or H-2Kd cDNA (B16/IFN-γ or B16/Kd cells) were used as controls. The B16/Kd/IFN-γ cells secreted biologically active IFN-γ, and strongly expressed both syngeneic and allogeneic MHC class I antigens (H-2Kb and H-2Kd) on the same cell construct. Immunization with the doubly transfected B16/Kd/IFN-γ cells induced higher anti B16F10 cellular cytotoxic responses than the single transfected B16/IFN-γ or B16/Kd 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 with the B16/Kd/IFN-γ cells, as demonstrated by in vitro depletion experiments. The survival period of melanoma-bearing mice treated with the B16/Kd/IFN-γ cells was significantly longer than that treated with the B16/IFN-γ or B16/Kd cells. Furthermore, the treatment with the B16/Kd/IFN-γ cells was capable of greatly inhibiting lung metastasis from small, established B16F10 footpad tumors. These results suggest that the augmented immunotherapeutic potentials can be achieved by the vaccination with IFN-γ and allogeneic MHC class I genes transfected B16F10 melanoma cells.