[GM3 ganglioside as melanoma specific antigen and its biological function]

We have shown that a syngenic monoclonal antibody, M2590, established after immunization of C57BL/6 mice with B16 melanoma cells, recognized GM3 (NeuAc) ganglioside. Although GM3 is widely distributed among various normal cells and tissues, the antibody did not react with them. However, it reacted exclusively with melanoma cells from mouse, hamster and human. Preliminary experiments suggested that proteins and lipids as well as GM3 density on B16 cells are involved in the reactivity of GM3 with the antibody. Then, we investigated the biological function of the melanoma antigen, which was secreted from B16 cells into the culture medium. This soluble antigen was shown to suppress the positive immune responses by inhibiting CTL activity in the effector phase and by induction of specific suppressor T cells (Ts) that block CTL generation in the induction phase. Liposomes containing GM3 (NeuAc) but not GM3 (NeuGc) can effectively induce the melanoma specific Ts as did the soluble antigen. The results indicated the tumor cells can escape from host-immune system by stimulating the repertoire of Ts for self-antigen, GM3. To understand the biological role of GM3, we have established mutant clones of no-expressor of GM3 recognized by M2590. The clones were found to have lower attachment to laminin and type IV collagen and poor ability of lung metastasis.