HER2 as a Promising Target for Cytotoxicity T Cells in Human Melanoma Therapy----中国科学院微生物研究所

科研成果

论文题目:	HER2 as a Promising Target for Cytotoxicity T Cells in Human Melanoma Therapy
作者:	Ma Juan, Han Huamin, Liu Deruo, Li Wei, Feng Hongxiang, Xue Xin, Wu Xiaoran, Niu Ge, Zhang Ge, Zhao Yunfeng, Liu Changzhen, Tao Hua, Gao Bin*
联系作者:	Gao Bin*
刊物名称:	Plos One
期:	8
卷:	8
页:
年份:	2013
影响因子:	4.244
论文下载:	http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0073261
摘要:	Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-gamma than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin(R)) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.