Disialoganglioside GD2 anti-idiotypic monoclonal antibodies.
Disialoganglioside GD2 is widely expressed among neuroblastomas, melanomas, small-cell lung carcinoma, sarcomas and brain tumors. Immunity directed against this antigen may have anti-tumor utility. Since GD2 is poorly immunogenic, anti-idiotypic antibodies may serve as alternative tumor vaccines. Monoclonal antibody 3F8, a murine IgG3 specific for GD2, has shown excellent tumor-targeting ability in vitro and in vivo. LOU/CN rats were immunized with 3F8 and their spleens were used in somatic-cell hybridization, using SP2/0, P3 and Y3 as fusion partners. Six anti-idiotypic (anti-id) MAbs (C2D8, Idio-2, AIG4, C2H7, C4E4, A2A6) were selected based on their reactivity with 3F8 and non-reactivity with murine IgG3 myelomas. Specificity of each anti-id was demonstrated by using various ELISA: (i) lack of direct binding to solid phase myelomas and serum proteins; (ii) inability of other myelomas to inhibit anti-id binding to 3F8; (iii) absence of cross-reactivity of other myelomas to solid-phase anti-id; (iv) lack of inhibition by anti-id of binding of other ganglioside antibodies to their antigens. Antigen specificity was further examined by inhibition of binding of 3F8 to GD2 on immuno-thin-layer chromatography, and by inhibition of 3F8 immunostaining of neuroblastoma cell lines. These 6 antibodies were demonstrated to be distinct, in view of their cross-reactivity, fusion partners and relative strength of binding to 3F8. Anti-GD2 antibodies were induced after immunization with these anti-id antibodies in C57Bl/6 mice. These rat anti-3F8-idiotypic antibodies with exquisite specificity for anti-GD2 antibodies may be useful in vaccine construction.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10021.
N K
NK
Cheung
A
A
Canete
I Y
IY
Cheung
J N
JN
Ye
C
C
Liu
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005678:G(M2) Ganglioside / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009194:Myeloma Proteins / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D005732:Gangliosides; D009194:Myeloma Proteins; D005678:G(M2) Ganglioside; C019403:ganglioside, GD2