title: HER2 as a promising target for cytotoxicity T cells in human melanoma therapy.
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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.forename: Huamin
authors.initials: H
authors.lastname: Han
authors.forename: Deruo
authors.initials: D
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Feng
authors.forename: Xin
authors.initials: X
authors.lastname: Xue
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Wu
authors.forename: Ge
authors.initials: G
authors.lastname: Niu
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Changzhen
authors.initials: C
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Tao
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D000912:Antibodies, Neoplasm; D017252:CD3 Complex; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human