Target level blocking of T-cell cytotoxicity for human malignant melanoma by monoclonal antibodies |
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Authors: | Alexander Knuth Wolfgang Dippold Karl-Hermann Meyer zum Bueschenfelde |
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Institution: | I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universitaet Mainz, Langenbeckstrasse 1, D 6500 Mainz, Federal Republic of Germany |
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Abstract: | 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 (γ3), specific for the GD3 disialoganglioside on melanoma cell surfaces and I24 (γM), 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. |
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