Target level blocking of T-cell cytotoxicity for human malignant melanoma by monoclonal antibodies.
Cytotoxic T lymphocytes (CTL) for autologous malignant melanoma in culture of a patient AV were induced by restimulation of PBL (peripheral blood leukocytes) with AV melanoma cells in vitro and subcultured in interleukin 2 (IL-2) conditioned media. Monoclonal antibodies detecting six antigenic systems on melanoma cell surfaces were tested for blocking activity on the effector function of subcultured cytolytic T lymphocytes for autologous melanoma cells. The monoclonal antibodies R24 (gamma 3), specific for the GD3 disialoganglioside on melanoma cell surfaces and I24 (gamma M), detecting a similar antigenic determinant, blocked autologous T lymphocytotoxicity for malignant melanoma cells on the target level. The effector function of alloantigen activated cytolytic T lymphocytes generated by coculture of allogeneic PBL with Epstein-Barr virus (EBV) transformed AV B lymphocytes, was blocked by monoclonal antibody R24 when tested against AV melanoma targets, but not when tested against AV B lymphocyte targets. It is concluded that blocking by mAb R24 occurs in this system as a nonspecific effect, unrelated to the specific target antigen recognition by cytotoxic T lymphocytes. Steric hindrance or antibody induced membrane changes may account for the blocking effect of monoclonal antibody R24.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007680:Kidney Neoplasms / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D007519:Isoantigens