title: Immunization of melanoma patients with BEC2 anti-idiotypic monoclonal antibody that mimics GD3 ganglioside: enhanced immunogenicity when combined with adjuvant.
abstract: Previous attempts to immunize melanoma patients against GD3 ganglioside have been unsuccessful because of the poor immunogenicity of GD3. BEC2, an anti-idiotypic monoclonal antibody that mimics GD3, can induce anti-GD3 IgG in rabbits. Since clinical trials with BEC2 in melanoma patients demonstrated that BEC2 alone is not highly immunogenic, we have carried out sequential clinical trials exploring the use of two immunological adjuvants, BCG and QS21, administered with BEC2. Melanoma patients free of disease after surgical resection but at high risk for recurrence were immunized either with BEC2/BCG (14 patients) or BEC2/QS21 (6 patients). All patients developed high-titer IgG antibodies against BEC2, demonstrating that both adjuvants effectively enhanced the immunogenicity of BEC2. Anti-GD3 antibodies were induced in 3 of 14 patients immunized with BEC2/BCG; no patient immunized with BEC2/QS21 developed detectable anti-GD3 antibodies. After a median follow-up of 2.4 years, 71% of the patients immunized with BEC2/BCG remain alive and 64% are free of disease. In patients immunized with BEC2/BCG, no apparent association was observed between class II HLA type and either development of anti-GD3 antibodies or survival. We are encouraged by the results with BEC2/BCG, which suggest that further enhancement of the immune response to BEC2 will result in more frequent anti-GD3 antibody responses among immunized patients.
authors.affiliation: Clinical Immunology Service, Department of Medicine and Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: M
authors.initials: M
authors.lastname: McCaffery
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: L
authors.initials: L
authors.lastname: Williams
authors.forename: P O
authors.initials: PO
authors.lastname: Livingston
authors.forename: A N
authors.initials: AN
authors.lastname: Houghton
authors.forename: P B
authors.initials: PB
authors.lastname: Chapman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D005260:Female; D005732:Gangliosides / Q000276:immunology; D005802:Genes, MHC Class II; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology; D011817:Rabbits; D015996:Survival Rate
chemical_list: D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D005732:Gangliosides; D006683:HLA-DQ Antigens; D007074:Immunoglobulin G; C026226:ganglioside, GD3