J. Biochem, 1990, Vol. 108, No. 1 109-115
© 1990 Japanese Biochemical Society
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Monoclonal Antibodies to Disialogangliosides: Characterization of Antibody-Mediated Cytotoxicity against Human Melanoma and Neuroblastoma Cells In Vitro1
*Department of Tumor Immunology, The Tokyo Metropolitan Institute of Medical Science Bunkyo-ku, Tokyo 113
**Department of Pathology, Tokai University School of Medicine Isehara, Kanagawa 250-11
***Meiji Institute of Health Science Odawara, Kanagawa 250
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 Fc-receptors (III), as well as having specificities towards multiple ganglioside antigens, possess the strongest cytotoxicity against human tumor cells in ADCC.
1This work was supported in part by a grant from the Science and Technology Agency of Japan and by a Grant-in-aid for Cancer Research and a Grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
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