Ganglioside GM2 expression on human melanoma cells correlates with sensitivity to lymphokine‐activated killer cells

Ganglioside GM2 is expressed on cell surface membranes of a variety of human malignant cells and has been demonstrated to be immunogenic in humans. We have assessed the role of the antigen GM2 on melanoma cells as a recognition structure for lymphokine‐activated killer (LAK) cells. LAK cells were generated by stimulation of non‐adherent peripheral blood lymphocytes (PBL) from human donors with recombinant interleukin‐2 (IL‐2). The selection of target cells was based on GM2 content and included II human melanoma cell lines and 2 human leukemia lines. Using a single‐cell binding assay, LAK cell binding to target lines expressing high levels of GM2 was significantly greater than to those expressing minimum GM2. This cell‐binding was specifically inhibited by addition of purified GM2 but not by other gangliosides. LAK‐melanoma cell‐binding was also specifically inhibited by anti‐GM2 monoclonal antibody (MAb). For further analysis LAK cell lysis of melanoma target cells expressing various amounts of GM2 was assessed. A significant correlation occurred with GM2 expression and LAK cell lysis (p < 0.025; r = 0.623). Three other gangliosides commonly expressed on human melanoma, GM3, GD3 and GD2, had no correlation with LAK cell lysis. These studies suggest that GM2 on melanoma cells is a marker for LAK cell sensitivity, as well as indicate that GM2 is a potential target recognition structure for human LAK cells.