New anti-GD2 monoclonal antibodies produced from gamma-interferon-treated neuroblastoma cells.
Three monoclonal antibodies (IgG2) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gamma-interferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectoderm-derived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 125I-labelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.
Gross
N
N
Department of Pediatrics, CHUV, Lausanne, Switzerland.
Beck
D
D
Portoukalian
J
J
Favre
S
S
Carrel
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification; D000951:Antigens, Neoplasm / Q000032:analysis; D001666:Binding Sites, Antibody / Q000187:drug effects; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D005732:Gangliosides / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology; D007114:Immunization / Q000379:methods; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D005732:Gangliosides; D007132:Immunoglobulin Isotypes; C019403:ganglioside, GD2; D007371:Interferon-gamma; D003165:Complement System Proteins