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KMID : 0578319980080050629
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Molecules and Cells
1998 Volume.8 No. 5 p.629 ~ p.636
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Augmentation of Therapeutic antitumor Immunity by B16f10 Melanoma Cells Transfected with Interferon-γ and Allogeneic MHC Class I cDNAs
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Lim, young Shin
Kang, Bok Yun/Kim, Eui Jin/Kim, Seung Hyun/Hwang, Seung Yong/Kim, Tae sung
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Abstract
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The cDNAs for interferon-γ (IFN-γ) and allogeneic H-2K^(d) molecules 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-γ cells) were investigated in C57BL/6 mice (H-2^(b)). The singly transfected B16F10 cells with either IFN-γ or H-2K^(d) cDNA (B16/IFN-γ or B16/K^(d) cells) were used as controls. The B16/K^(d)/IFN-γ cells secreted biologically active IFN-γ, and strongly expressed both syngeneic and allogeneic MHC class Ⅰ antigens (H-2K^(d) and H-2K^(d)) on the same cell construct. Immunization with the doubly transfected B16/K^(d)/IFN-γ cells induced the higher anti B16F10 cellular cytotoxic responses than the single transfected. B16/IFN-γ 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 with the B16/K^(d)/IFN-γ cells, as demonstrated by in vitro depletion experiments. The survival period of melanoma-bearing mice treated with the B16/K^(d)/IFN-γ cells was significantly longer than that treated with the B16/IFN-γ or B16/K^(d) cells. Furthermore, the treatment with the B16/K^(d)/IFN-γ cells was capable of greatly inhibiting lung metastasis from small, established B16F10 footpad tumors.l These results suggest that the augmented immunotherapeutic potentials can be achieved by the vaccination with IFN-γ and allogeneic MHC class Ⅰ genes transfected B26F10 melanoma cells.
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