HER2 as a promising target for cytotoxicity T cells in human melanoma therapy
Juan Ma, Huamin Han, Deruo Liu, Wei Li, Hongxiang Feng, Xin Xue, Xiaoran Wu, Ge Niu, Ge Zhang, Yunfeng Zhao, Changzhen Liu, Hua Tao, Bin Gao, Juan Ma, Huamin Han, Deruo Liu, Wei Li, Hongxiang Feng, Xin Xue, Xiaoran Wu, Ge Niu, Ge Zhang, Yunfeng Zhao, Changzhen Liu, Hua Tao, Bin Gao
Abstract
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-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) 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.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
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References
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