ANALYSIS OF THE ANTIBODY-RESPONSE TO IMMUNIZATION WITH PURIFIED O-ACETYL GD3 GANGLIOSIDES IN PATIENTS WITH MALIGNANT-MELANOMA

Gangliosides expressed in malignant melanoma are potential targets for immunotherapy. Immunization of melanoma patients with vaccines contai ning purified GM2 ganglioside has resulted in induction of GM2 antibod ies, and high titers of GM2 antibodies have correlated with increased survival. Melanoma ganglioside 9-O-acetyl GD3 is another candidate for ganglioside vaccine construction because of its limited expression in normal human tissues. As purification of 9-O-acetyl GD3 from human me lanoma (9-O-acetylated on the terminal sialic acid) is not practical f or broad application, we investigated the antibody response of melanom a patients to O-acetyl GD3 from several additional sources: hamster me lanoma (7-O-acetyl GD3), bovine buttermilk (mixture of 7-O-acetyl GD3, 9-O-acetyl GD3 and 7,9-di-O-acetyl GD3) and chemically modified GD3 f rom bovine brain (9-O-acetylated on the subterminal sialic: acid). Onl y immunization with the buttermilk-derived O-acetyl GD3 preparation re sulted in consistent production of IgM antibodies. However, the induce d antibodies reacted with the immunogen and with 7-O-acetyl GD3 derive d from hamster melanoma but not with 9-O-acetyl GD3 or human melanoma cells expressing 9-O-acetyl GD3 on their cell surface. In contrast, al l O-acetyl GD3 derivatives used for immunization were recognized by mu rine MAbs that reacted with 9-O-acetyl GD3, and immunization of mice w ith buttermilk-derived O-acetyl GD3 resulted in the production of anti bodies that reacted with human melanoma cells expressing 9-O-acetyl GD 3, Apparently, the human and murine immune systems preferentially reco gnize different epitopes on these molecules. (C) 1995 Wiley-Liss, Inc.