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Reversal of adriamycin resistance with chimeric anti‐ganglioside G M2 antibody
Author(s) -
Fukumoto Hisao,
Nishio Kazuto,
Ohta So,
Hanai Nobuo,
Saijo Nagahiro
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960904)67:5<676::aid-ijc14>3.0.co;2-3
Subject(s) - ganglioside , antibody , medicine , resistance (ecology) , immunology , virology , biology , genetics , ecology
Ganglioside G M2 is one of the major cell‐surface gangliosides expressed in human tumors. We earlier established a mouse/human IgGI chimeric anti‐G M2 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 G M2 expression, detected by flow cytometry and thin‐layer chromatography, was observed in the SBC‐3/ADM and AdrR MCF7 adriamycin‐resistant cell lines, in contrast with their parental lines. In other related gangliosides, ganglioside G D2 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 Northern‐blot analysis. Moreover, to investigate the possibility of exploiting the anti‐tumor activity of KM966 in order to overcome resistance to adriamycin, we investigated the antibody‐dependent cell‐mediated cytotoxity of human peripheral mononuclear blood cells and the complement‐dependent cytotoxity of human serum with KM966 against SBC‐3, SBC‐3/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. © 1996 Wiley‐Liss, Inc.