The immunogenic properties of human melanomas and melanoma-associated antigens recognized by cytotoxic T lymphocytes.

During the last years significant progress has been achieved in the identification of melanoma-associated antigens (MAA) recognized by cytotoxic T lymphocytes (CTL). These antigens belong to three main groups: tumor-associated testis-specific antigens (MAGE, BAGE, GAGE and PRAME), melanocyte differentiation antigens (tyrosinase, Melan-A/MART-1, gp100, TRP-1 and TRP-2) and mutated or aberrantly expressed antigens (MUM-1, CDK4, beta-catenin, gp100-in4, p15 and N-acetylglucosaminyltransferase V). For the identification of these antigens, CTL cultures from mainly only 4 different melanoma patients have been used. These patients developed a strong anti-melanoma response resulting in long-lasting disease-free periods, pointing to the importance of the identification of highly immunogenic melanomas. In each of these patients, the immune response was observed against a unique set of 4 to 6 individual antigenic epitopes, on one hand suggesting the low immunogenicity of the individual antigens, and on the other pointing to the importance of the identification of additional highly immunogenic melanomas for the discovery of new MAA. The analysis of the available data on the immunogenic and protective properties of individual MAA confirms their low immunogenicity. In our study, we focused on the identification of especially highly immunogenic melanomas among a panel of 40 newly established melanoma cell lines. So far, only two such melanoma cell lines, FM3 and FM57 have been identified in this panel. The immunogenic properties of uncloned FM3 cells and several FM3 clones have been further investigated. It was found that the immunogenic properties of melanoma cells are mainly determined by the expression of progression-associated antigens as well as by ecto-ATPase, a molecule which is able to modulate cell adhesion. Cloning the cultures of PBL, stimulated with uncloned FM3 or with the highly immunogenic FM3 clone, FM3.29, has permitted us to identify the immune response against eight different MAA, five of these probably representing not previously described antigens. (Tab. 2, Fig. 2, Ref. 68.)