Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection.

Abstract

Cytolytic T-lymphocyte (CTL) clones against an autologous melanoma (SK-MEL-29) were generated by mixed lymphocyte tumor culture and subsequent cloning of responder lymphocytes at limiting dilutions. These CTL clones lysed autologous melanoma but not autologous Epstein-Barr virus-transformed B cells and none of the allogeneic tumor targets included in the specificity analysis. The lysis of autologous melanoma targets could be inhibited by monoclonal antibodies against monomorphic HLA class I determinants. For proliferation of CTLs, the stimulation with the relevant target antigen on autologous tumor cells was essential. Immunoselection experiments carried out with two CTL clones revealed the existence of melanoma subclones that were resistant to lysis by the CTL clones used for immunoselection but were still lysed by other autologous CTL clones. This analysis allowed us to identify three stable simultaneously expressed antigens on the melanoma cells defimed by autologous CTLs.The search for human cancer antigens eliciting a specific autologous immune response has been pursued with serum antibodies and T lymphocytes. The most compelling evidence to date for the existence of tumor antigens eliciting a specific autologous antibody response in patients comes from studies of Old and colleagues (1-3), demonstrating serum autoantibodies that were specific for the autologous cancer cells. Several groups obtained cytolytic T-lymphocyte (CTL) clones that showed specificity for the autologous tumor cells (4-8). We have developed techniques for the systematic production of stable CTL clones directed against autologous melanoma cells (9). In a study of a melanoma patient, MZ-2, three antigens were identified with autologous CTL clones: antigen A was present on all melanoma clones tested, antigen B could be lost during long-term culture, and antigen C was only expressed on a minority of melanoma clones (9).We report here a specificity study of autologous CTL clones obtained against a melanoma SK-MEL-29 from a patient AV. Through immunoselection with CTL clones we were able to define three stable antigens on this melanoma. MATERIALS AND METHODS

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