Hancock M C, Langton B C, Chan T, Toy P, Monahan J J, Mischak R P, Shawver L K
Department of Cell Biology and Immunology, Berlex Biosciences, Inc., Alameda, California 94501.
Cancer Res. 1991 Sep 1;51(17):4575-80.
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.
一种针对c-erbB-2蛋白（gp185）细胞外表位的单克隆抗体（TAb 250），以剂量依赖方式抑制了过表达c-erbB-2的人乳腺肿瘤细胞系的体外增殖。用顺二氯二氨铂（CDDP）和TAb 250联合处理细胞，可显著增强细胞毒性作用。这种协同细胞毒性在很宽的抗体浓度范围（200 pg/ml - 100 μg/ml）内都很明显，包括单独使用时无抑制作用的浓度。在一个未检测到gp185水平的细胞系中，TAb 250并未增加CDDP的细胞毒性作用。与单独使用抗体或CDDP相比，用人肿瘤细胞高水平表达gp185的皮下异种移植物的无胸腺小鼠，在用TAb 250和CDDP处理时，肿瘤生长的抑制作用大大增强。这种作用具有特异性，因为TAb 250并未增强CDDP对不表达gp185的肿瘤异种移植物的生长抑制作用。
