HER2 as a promising target for cytotoxicity T cells in human melanoma therapy

• Published in: PloS one 2013-08, Vol.8 (8), p.e73261
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Bispecific - immunology; Antibodies, Bispecific - pharmacology; Antibodies, Neoplasm - immunology; Antibodies, Neoplasm - pharmacology; Anticancer properties; Biophysics; Bispecific antibodies; Breast cancer; Cancer therapies; CD3 antigen; CD3 Complex - immunology; CD3 Complex - metabolism; CD69 antigen; Cell culture; Cell proliferation; Cytolytic activity; Cytotoxicity; Effector cells; ErbB-2 protein; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - immunology; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - immunology; Growth factors; Humans; Immunology; Immunotherapy; Interferon; K562 Cells; Kinases; Laboratories; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Melanoma; Melanoma - drug therapy; Melanoma - immunology; Melanoma - pathology; Metastasis; Mice; Mice, SCID; Monoclonal antibodies; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - immunology; Receptor, ErbB-2 - metabolism; Surgery; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Therapy; Thoracic surgery; Toxicity; Tumor cells; Tumors; Xenograft Model Antitumor Assays; Xenografts; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073261

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.