The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.

TLDR

Melanoma patients’ lymphocytes can be restimulated with autologous tumor cells to generate antitumor CTL that show broad reactivity against HLA‑A2 melanoma cell lines. The study reports cloning the cDNA encoding the antigen recognized by these CTL and emphasizes the need to evaluate potential adverse effects of antityrosinase immunization before clinical trials. The authors isolated antitumor CTL clones from two patients that recognize a shared antigen. The cloned cDNA encodes tyrosinase, which is expressed in all tested melanomas and most melanoma cell lines but only in melanocytes among normal tissues, making the tyrosinase antigen presented by HLA‑A2 a promising target for melanoma immunotherapy.

Abstract

Lymphocytes of melanoma patients can be restimulated in vitro with autologous tumor cells to generate antitumor cytolytic T lymphocytes (CTL). Previous reports have indicated that, when such CTL are obtained from HLA-A2 melanoma patients, they often display broad reactivity on A2 melanoma cell lines. Such antitumor CTL clones, which appeared to recognize the same antigen, were isolated from two patients. We report here the cloning of a cDNA that directs the expression of the antigen recognized by these CTL. This cDNA corresponds to the transcript of the tyrosinase gene. The gene was found to be active in all tested melanoma samples and in most melanoma cell lines. Among normal cells, only melanocytes appear to express the gene. The tyrosinase antigen presented by HLA-A2 may therefore constitute a useful target for specific immunotherapy of melanoma. But possible adverse effects of antityrosinase immunization, such as the destruction of normal melanocytes and its consequences, will have to be examined before clinical pilot studies can be undertaken.