Human monoclonal antibody to tumor-associated ganglioside GD2: suppressed growth of human melanoma in nude mice

Human IgM kappa monoclonal antibody (anti-GD2) to a tumor antigen, ganglioside GD2, has been produced by Epstein-Barr virus-transformed human B lymphoblasts. In the present study, we demonstrated the anti-tumor effects of passively administered anti-GD2 against an ascites-form human melanoma cell line, M14-A, transplanted into athymic nude mice. M14-A expresses GD2 in vivo. Cells (5 X 10(5) were inoculated intraperitoneally (i.p.) or subcutaneously (s.c.) into CD-1 nude mice that had received i.p. injections of 200 micrograms anti-GD2 and rabbit complement. Significant tumor-free intervals were observed in the treated mice (P less than 0.005) for i.p. tumors and P less than 0.025 for s.c. tumors). M14-A formed well-vascularized s.c. tumors if injected into young nude mice. Three-wk-old CD-1 nude mice bearing 2-3 mm M14-A s.c. tumor nodules were treated i.p. with anti-GD2 and rabbit complement. Tumor growth was delayed for 25 days. On day 15, treated tumors were 20% the size of control tumors. Because most biopsied or autopsied melanomas express GD2, and because patients with melanoma produce autoantibodies to GD2, the results in this study may provide important information for future passive immunization with human monoclonal antibody and for active specific immunization with GD2 antigen.