| 论文题目: | HER2 as a Promising Target for Cytotoxicity T Cells in Human Melanoma Therapy |
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| 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: | 下载地址 |
| 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. |
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