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 11 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 less than 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.
Hoon
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DS
Division of Surgical Oncology, Armand Hammer Laboratories, John Wayne Cancer Clinic, UCLA School of Medicine 90024.
Ando
I
I
Sviland
G
G
Tsuchida
T
T
Okun
E
E
Morton
D L
DL
Irie
R F
RF
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005678:G(M2) Ganglioside / Q000096:biosynthesis* / Q000302:isolation & purification; D005732:Gangliosides / Q000096:biosynthesis*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D008563:Membrane Lipids / Q000096:biosynthesis* / Q000302:isolation & purification; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D008222:Lymphokines; D008563:Membrane Lipids; D005678:G(M2) Ganglioside