IMMUNIZATION OF MELANOMA PATIENTS WITH BEC2 ANTIIDIOTYPIC MONOCLONAL-ANTIBODY THAT MIMICS GD3 GANGLIOSIDE - ENHANCED IMMUNOGENICITY WHEN COMBINED WITH ADJUVANT

Previous attempts to immunize melanoma patients against GD3 gangliosid e have been unsuccessful because of the poor immunogenicity of GD3, BE C2, an anti-idiotypic monoclonal antibody that mimics GD3, can induce anti-GD3 IgG in rabbits, Since clinical trials with BEC2 in melanoma p atients demonstrated that BEC2 alone is not highly immunogenic, we hav e carried out sequential clinical trials exploring the use of two immu nological adjuvants, BCG and QS21, administered with BEC2, Melanoma pa tients free of disease after surgical resection but at high risk for r ecurrence were immunized either with BEC2/BCG (14 patients) or BEC2/QS 21 (6 patients), All patients developed high-titer IgG antibodies agai nst BEC2, demonstrating that both adjuvants effectively enhanced the i mmunogenicity of BEC2. Anti-GD3 antibodies were induced in 3 of 14 pat ients immunized with BEC2/BCG; no patient immunized with BEC2/QS21 dev eloped detectable anti-GD3 antibodies, After a median follow-up of 2.4 years, 71% of the patients immunized with BEC2/BCG remain alive and 6 4% are free of disease, In patients immunized with BEC2/BCG, no appare nt association was observed between class II HLA type and either devel opment of anti-GD3 antibodies or survival, We are encouraged by the re sults with BEC2/BCG, which suggest that further enhancement of the imm une response to BEC2 will result in more frequent anti-GD3 antibody re sponses among immunized patients.