A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines.
A monoclonal antibody (TAb 250) specific to an extracellular epitope of the c-erbB-2 protein (gp185) inhibited the in vitro proliferation of human breast tumor cell lines that overexpress c-erbB-2 in a dose-dependent manner. Treatment of cells with combinations of cis-diammedichloroplatinum (CDDP) and TAb 250 resulted in a significantly enhanced cytotoxic effect. This synergistic cytotoxicity was apparent over a wide range of antibody concentrations (200 pg/ml-100 micrograms/ml) including concentrations that showed no inhibitory effect alone. TAb 250 did not increase the cytotoxic effect of CDDP in a cell line exhibiting no detectable level of gp185. Athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of gp185 showed a greatly enhanced inhibition of tumor growth when treated with TAb 250 and CDDP compared to treatment with the antibody or CDDP alone. This effect was specific inasmuch as TAb 250 did not enhance the growth-inhibitory effect of CDDP on tumor xenografts which were not expressing gp185.
Hancock
M C
MC
Department of Cell Biology and Immunology, Berlex Biosciences, Inc., Alameda, California 94501.
Langton
B C
BC
Chan
T
T
Toy
P
P
Monahan
J J
JJ
Mischak
R P
RP
Shawver
L K
LK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000302:isolation & purification; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases
D000911:Antibodies, Monoclonal; D002945:Cisplatin; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases