Immunorecognition of ganglioside epitopes: correlation between affinity and cytotoxicity of ganglioside antibodies.
Cell-surface gangliosides have immunomodulatory effects that are presumed to play a role in tumour growth, progression, metastasis and therapy. To study the epitopes of gangliosides on human malignant melanomas and to search for monoclonal antibodies (Mabs) with superior immunological effector functions, 19 ganglioside antibodies were established. Specificity and affinity of nine antibodies of IgG3 isotype were evaluated by enzyme linked immunosorbent assay and thin layer chromatography with a panel of purified gangliosides. All antibodies recognised the ganglioside GD3, but their epitope specificity divided them into five groups. Their affinity constants for ganglioside GD3 ranged from 4.7 x 10(6) to 2.3 x 10(8), with 2 x 10(7) for Mab R-24. Two antibodies possessed a higher affinity for GD2 than for GD3. The functional properties of the antibodies were investigated in vitro. Differences in the degree of tumour lysis by complement fixation correlated with the affinity constants. Every ganglioside antibody differed in epitope recognition, affinity and cytotoxicity. Therefore some of these antibodies might even be more useful in the immunotherapy of malignant melanoma than Mab R-24.
Dippold
W
W
Medizinische Klinik, Johannes Gutenberg-Universität, Mainz, Germany.
Bernhard
H
H
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D002460:Cell Line; D002855:Chromatography, Thin Layer; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D005732:Gangliosides