IMMUNITY TO B16 MELANOMA IN MICE IMMUNIZED WITH IL-2-SECRETING ALLOGENEIC MOUSE FIBROBLASTS EXPRESSING MELANOMA-ASSOCIATED ANTIGENS

Co-presentation of weak tumour-associated antigens along with strongly immunogenic determinants leads to the development of an anti-tumour immune response in recipients syngeneic with the tumour. Tumour immunity develops in mice immunized with tumour cells modified by the introduction of cDNA for interleukin-2 (IL-2). Here, we report the anti-tumour response following immunization with an IL-2-secreting cell construct that expresses tumour-associated antigens, along with allogeneic major histocompatibility antigens. The construct was prepared by transfecting LM(TK-) mouse fibroblasts (H-2k) with genomic DNA from B 16 melanoma cells syngeneic in C57BL/6J mice (H-2b). Transfectants expressing melanoma-associated antigens (MAA) were then infected with an expression-competent retroviral vector containing a cDNA specifying human IL-2. Cytotoxicity toward B 1 6 cells was detected for as long as 5 months in both spleen and macrophage cell populations in C57BL/6J mice immunized with the IL-2-secreting cells. Mice immunized with non-IL-2-secreting, MAA-positive allogeneic cells developed melanoma immunity as well, but to a lesser extent. Immunity to 2 tumour-cell lines expressing the H-2d haplotype and to YAC-1 cells was detected in peritoneal macrophages, but not in spleen cells from C57BL/6J mice immunized with the cell construct, indicating that the response to B16 cells was only partially specific. C57BL/6J mice immunized with the IL-2-secreting cell construct survived significantly longer, following an injection of viable B16 cells, than mice in various control groups. The contribution of allogeneic antigens to the melanoma immunity was indicated by the failure of mice syngeneic with LM(TK-) cells to develop melanoma immunity following immunization with non-IL-2-secreting, MAA-positive cell constructs. The formation of IL-2 partially compensated for the lack of allogneic antigens.