Monoclonal antibodies to disialogangliosides: characterization of antibody-mediated cytotoxicity against human melanoma and neuroblastoma cells in vitro.
We previously reported the binding specificities of two anti-ganglioside GD2 murine monoclonal antibodies (MAbs), A1-425 and A1-267, both of which are of IgG3 isotype. A1-425 reacts specifically with ganglioside GD2, whereas A1-267 binds preferentially to GD2 but also reacts with GD3 [Tai, T., Kawashima, I., Tada, N., & Dairiki, K. (1988) J. Biochem. 103, 682-687]. In this paper, they were used for comparative analyses of antibody-mediated cytotoxicity, i.e., antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human melanoma and neuroblastoma cell lines. Melanoma cells were found to contain GD2 and/or GD3, whereas neuroblastoma cells expressed only GD2. Both antibodies induced high levels of ADCC and CDC to GD2/GD3-positive cells with human peripheral large granular lymphocytes (LGL) as effector cells and in the presence of human serum, respectively. A good correlation was obtained between the contents of disialogangliosides and the binding level of the antibodies; both melanoma and neuroblastoma cells with larger amounts of GD2/GD3 showed a higher level of antibody binding than did the cells with a smaller amount of GD2/GD3. Surprisingly, ADCC did not correlate well with the binding level of the antibodies. Thus, A1-425 showed stronger lytic activity than A1-267 in spite of the binding level of A1-425 being similar to or lower than that of A1-267 on the cell surfaces. Antigen-antibody complexes composed of GD2 and A1-425 showed higher binding levels to LGL than complexes of GD2 and A1-267. In contrast, free MAb molecules gave minimum binding to LGL.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawashima
I
I
Department of Tumor Immunology, Tokyo Metropolitan Institute of Medical Science.
Tada
N
N
Fujimori
T
T
Tai
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D001923:Brain Chemistry; D002417:Cattle; D002855:Chromatography, Thin Layer; D003601:Cytotoxicity Tests, Immunologic; D005732:Gangliosides / Q000276:immunology*; D006028:Glycosphingolipids / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D009447:Neuroblastoma / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D006028:Glycosphingolipids; D011961:Receptors, Fc