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Characterization of IgG and IgM Antibodies Induced in Melanoma Patients by Immunization with Purified G_M2 Ganglioside¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021

The ganglioside G_M2 is a differentiation antigen expressed on the cell surface of human malignant melanomas and other cancers of neuroectodermal origin. We have previously reported that immunization with purified G_M2 combined with Bacillus Calmette-Guérin as adjuvant and pretreatment with low-dose cyclophosphamide induced production of antibodies against G_M2 in five of six patients. We have now extended our study and analyzed the induced antibody response in greater detail. Prior to immunization, high-titer antibodies against G_M2 were not detected. After immunization, high-titer IgM antibodies were induced in 17 of 24 patients, and high-titer IgG antibodies in eight cases. Additional treatment of 12 patients with cimetidine, a histamine H2 receptor antagonist reported to have antisuppressor cell activity, had no effect on G_M2 antibody titers. Antibodies against asialo-G_M2 were present in all patients, and antibodies against G_M1 were present in 33% of patients, before and after immunization. Antibodies induced by immunization were specific for G_M2, though some reacted predominantly with N-acetylneuraminic acid G_M2 (G_M2), and some reacted with G_M2 and N-glycolylneuraminic acid G_M2(NeuGcG_M2). The pattern of reactivity with G_M2 is consistent with the response to T-cell-independent antigens: both IgM and IgG antibody responses against G_M2 were short lived; peak titers seen after initial and secondary vaccinations were similar; and delayed-type hypersensitivity responses to skin test challenges with G_M2 were not detected in any patients. However, the IgG response typed as predominantly IgG1 and IgG3, not IgG2 as might be expected for carbohydrate antigens (which are generally T-cell-independent antigens). Because IgG1 and IgG3 antibody responses are usually to T-cell-dependent antigens, the humoral immune response elicited by G_M2 vaccination has both T-cell-dependent and T-cell-independent characteristics. These IgM and IgG responses against this neuroectodermal differentiation antigen expressed on melanoma cells have been induced without evidence of neurological or other toxicity.

¹ This work was supported by grants from the Perkin Foundation, the Diamond Foundation, the National Cancer Institute (CA-40532, CA-08748), and a fellowship from the Deutsche Forschungemeinschaft (R:483/1-1).

² To whom requests for reprints should be addressed.

³ Present address: Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York, New York 10029.

Received 4/ 6/89. Revised 8/28/89. Accepted 9/18/89.