Immunization of mice with allogeneic fibroblasts genetically modified for interleukin-2-secretion and expression of melanoma-associated antigens stimulate predetermined classes of anti-melanoma effector cells.
Immunization of C57BL/6 mice (H-2b) with a mouse fibroblast cell-line of C3H origin (H-2k) genetically modified for interleukin-2 (IL-2)-secretion and the expression of melanoma-associated antigens (MAAs) (RLBA-IL-2 cells) resulted in a systemic anti-melanoma cellular immune response that led to a prolongation of survival of mice with established melanoma. Here we report certain of the effector cell-types activated for anti-melanoma immunity in mice immunized with the modified cells and, for comparison, the anti-melanoma cell-types activated following immunization with IL-2-secreting, MAA-negative fibroblasts (LM-IL-2 cells) or with non-IL-2-secreting, MAA-positive fibroblasts (RLBA-ZipNeo cells). The data indicate that both Lyt-2.2+ (CD8+) and natural killer/lymphokine-activated killer (NK/LAK) cells with anti-melanoma cytotoxicity were predominant in mice immunized with RLBA-IL-2 cells. NK/LAK cells alone were predominant in mice immunized with LM-IL-2 cells, and Lyt-2.2+ cells were predominant in mice immunized with RLBA-ZipNeo cells. The involvement of L3T4+ (CD4+) cells in the effector phase of the response was not detected in mice immunized with the genetically modified cells. Immunization of mice with both LM-IL-2 cells and RLBA-ZipNeo cells resulted in an anti-melanoma response of greater magnitude than was present in mice immunized with either cell-construct alone. It was equivalent to the melanoma immunity in mice immunized with RLBA-IL-2 cells. These data indicate that the immunogenic properties of the modified cells determined the anti-melanoma effector cell-types and suggest that combination immunotherapy with cell-constructs that stimulate different classes of effector cells may be more effective in immune-mediated tumor regression than immunization with a construct that activates a single effector cell-type alone.
Kim
T S
TS
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago.
Cohen
E P
EP
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D018014:Gene Transfer Techniques; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics; D016176:T-Lymphocyte Subsets; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm; D007376:Interleukin-2; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins