The Journal of Biochemistry
Online ISSN : 1756-2651
Print ISSN : 0021-924X
Monoclonal Antibodies to Disialogangliosides: Characterization of Antibody-Mediated Cytotoxicity against Human Melanoma and Neuroblastoma Cells In Vitro
Ikuo KawashimaNobuhiko TadaTakao FujimoriTadashi Tai
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1990 Volume 108 Issue 1 Pages 109-115

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Abstract

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. An anti-human Fc-receptors (III) MAb specifically inhibited both the binding of the antigen-antibody complex to LGL and the ADCC by the MAbs with LGL. These findings demonstrate that MAbs having high binding levels to Fcreceptors (III), as well as having specificities towards multiple ganglioside antigens, possess the strongest cytotoxicity against human tumor cells in ADCC.

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© The Japanese Biochemical Society
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