Reversal of adriamycin resistance with chimeric anti-ganglioside GM2 antibody

✍ Scribed by Hisao Fukumoto; Kazuto Nishio; So Ohta; Nobuo Hanai; Nagahiro Saijo

• Book ID: 102653641
• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 604 KB
• Volume: 67
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960904)67:5<676::aid-ijc14>3.0.co;2-3

✦ Synopsis

Ganglioside GH2 is one of the major cell-surface gangliosides expressed in human tumors. We earlier established a mouse/ human IgG I chimeric anti-GM2 antibody, KM966, which displayed anti-tumor activity in human tumor cells both in vitro and in vivo. In this study, we have screened for changes in ganglioside expressions in several drug-resistant human cancer cell lines to examine the modulation of drug resistance by immunotherapy with anti-ganglioside antibodies. Increased GM2 expression. detected by flow cytometry and thin-layer chromatography, was observed in the SBC-3/ADM and AdrR MCF7 adriamycinresistant cell lines, in contrast with their parental lines. In other related gangliosides, ganglioside GD2 levels in AdrR MCF7 were higher than those in MCF7 cells. We confirmed increased N-acetylgalactosaminyltransferase mRNA in adriamycin-resistant cell lines, as compared with the parental cells, by Northernblot analysis. Moreover, to investigate the possibility of exploiting the anti-tumor activity of KM966 in order to overcome resistance to adriarnycin, we investigated the antibodydependent cell-mediated cytotoxity of human peripheral mononuclear blood cells and the complement-dependent cytotoxity of human serum with KM966 against SBC-3, SBC-)/ADM, MCF7 and AdrR MCF7. Significantly higher killing via KM966 was observed in SBC-3/ADM and AdrR MCF7 cells as compared with the parental cells. This suggests that passive immunotherapy using KM966 against human adriamycin-resistant cancer may be useful for overcoming resistance to adriamycin. 0 1996 Wiley-