title: Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor.
abstract: Genetically modified T cells to recognize tumor-associated antigens by transgenic TCRs or chimeric antigen receptors (CAR) have been successfully applied in clinical trials. However, the disadvantages of either TCR mismatching or the requirement of a surface tumor antigen limit their wider applications in adoptive T cell therapy. A TCR-like chimeric receptor, specific for the melanoma-related gp100/HLA-A2 complex was created by joining a TCR-like antibody GPA7 with the endodomains of CD28 and CD3-ζ chain. This TCR-like CAR, GPA7-28z, was subsequently introduced into human T cells. Retargeted T cells expressing GPA7-28z could exhibit efficient cytotoxic activities against human melanoma cells in vitro in the context with HLA-A2. Furthermore, infusion of GPA7-28z-transduced T cells suppressed melanoma progression in a xenograft mouse model. Redirecting human T cells with TCR-like CARs would be a promising alternative approach to TCR-mediated therapy for melanoma patients, which is also feasible for targeting a variety of other tumor antigens.
authors.affiliation: 1] Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: 1] Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Honglian
authors.initials: H
authors.lastname: Cui
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 100010 Beijing, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, 100010 Beijing, China.
authors.forename: Ganlin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Huamin
authors.initials: H
authors.lastname: Han
authors.affiliation: Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, 050017 Shijiazhuang, China.
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1] Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
authors.forename: Changzhen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Epigen Biotec Ltd, 100101 Beijing, China.
authors.forename: Meiyi
authors.initials: M
authors.lastname: Sun
authors.affiliation: 1] Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins