An anti-idiotype vaccine elicits a specific response to N-glycolyl sialic acid residues of glycoconjugates in melanoma patients.
We generated the 1E10 gamma-type anti-idiotype mAb (Ab2) specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with Ags expressed on human melanoma and breast carcinoma cells. This Ab2 mAb induced an Ab response in animal models sharing immunochemically defined idiotopes with the Ab1. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. A clinical trial was conducted in 20 patients with advanced malignant melanoma. Patients were treated with six intradermal injections of aluminum hydroxide-precipitated 1E10 anti-Id mAb given at 2-wk intervals. Sixteen of the 17 patients who received at least four doses of the anti-Id vaccine develop Ab3 Abs capable of inhibiting Ab2 binding to Ab1 (Ab3Id+). In contrast to the incapacity of 1E10 mAb to generate Ab3 Abs with the same antigenic specificity as the Ab1 mAb in mice, a very specific and strong Ab3 response against N-glycolyl-containing gangliosides was induced in 16 patients (Ab3Ag+). No evidence of serious or unexpected adverse effects has been observed in this clinical trial. 1E10 anti-Id vaccine was safe, well tolerated, and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and Neu-glycolyl-GM(3) ganglioside.
Alfonso
Mauro
M
Department of Antibody Engineering, Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba. mauro@ict.cim.sld.cu
Díaz
Alain
A
Hernández
Ana María
AM
Pérez
Alexis
A
Rodríguez
Edmundo
E
Bitton
Roberto
R
Pérez
Rolando
R
Vázquez
Ana María
AM
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001667:Binding, Competitive; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D005679:G(M3) Ganglioside / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D019158:N-Acetylneuraminic Acid