Co-expression of immunogenic determinants by the same cellular immunogen is required for the optimum immunotherapeutic benefit in mice with melanoma.
Tumor-associated T cell epitopes are recognized by T cells in the context of determinants specified by class I loci. Since the rejection of foreign histocompatibility antigens is known to enhance tumor immunity, immunization with a cellular vaccine that combined the expression of both syngeneic and allogeneic class I determinants could have important immunological advantages over a vaccine that expressed either syngeneic or allogeneic determinants alone. To investigate this question in a mouse melanoma model system, we tested the immunotherapeutic properties of B16 melanoma x LM fibroblast hybrid cells in C57BL/6J mice with melanoma. Like C57BL/6J mice, B16 cells expressed H-2Kb class I determinants and (antibody-defined) melanoma-associated antigens. LM cells, of C3H mouse origin, formed H-2Kk determinants along with B7.1, a co-stimulatory molecule that can activate T cells. The B16 x LM hybrid cells co-expressed H-2Kb and H-2Kk class I determinants, B7.1 and the melanoma-associated antigens. C57BL/6J mice with melanoma, immunized with the semi-allogeneic hybrid cells, developed CD8-mediated melanoma immunity and survived significantly (P < 0.005) longer than mice with melanoma immunized with a mixture of the parental cell types. The failure of melanoma immunity to develop in mice injected with the mixture of parental cells indicated that co-expression of the immunogenic determinants by the same cellular immunogen was necessary for an optimum immunotherapeutic effect. Augmented immunity to melanoma in mice immunized with the semi-allogeneic hybrid cells points toward an analogous form of therapy for patients with melanoma.
Xu
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Department of Microbiology and Immunology (M/C 790), Chicago, IL 60612, USA.
de Zoeten
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Carr-Brendel
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V
Cohen
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EP
D000818:Animals; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006822:Hybrid Cells; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014614:Vaccines, Synthetic