title: Specificity redirection by CAR with human VEGFR-1 affinity endows T lymphocytes with tumor-killing ability and anti-angiogenic potency.
abstract: Immunotherapy that is based on adoptive transfer of T lymphocytes, which are genetically modified to express chimeric antigen receptors (CARs) that recognize tumor-associated antigens, has been demonstrated to be an efficient cancer therapy. Vascular endothelial growth factor receptor-1 (VEGFR-1), a vital molecule involved in tumor growth and angiogenesis, has not been targeted by CAR-modified T lymphocytes. In this study, we generated CAR-modified T lymphocytes with human VEGFR-1 specificity (V-1 CAR) by electroporation. V-1 CAR-modified T lymphocytes were demonstrated to elicit lytic cytotoxicity to target cells in a VEGFR-1-dependent manner. The adoptive transfer of V-1 CAR T lymphocytes delayed tumor growth and formation and inhibited pulmonary metastasis in xenograft models and such efficacies were enhanced by cotransfer of T lymphocytes that expressed interleukin-15 (IL-15). Moreover, V-1 CAR-modified T lymphocytes lysed primary endothelial cells and impaired tube formation, in vitro. These data demonstrated the antitumor and anti-angiogenesis ability of V-1 CAR-modified T lymphocytes. Our study provides the rationale for the clinical translation of CAR-modified T lymphocytes with VEGFR-1 specificity.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors: W
authors: W
authors: Wang
authors: Y
authors: Y
authors: Ma
authors: J
authors: J
authors: Li
authors: H-S
authors: HS
authors: Shi
authors: L-Q
authors: LQ
authors: Wang
authors: F-C
authors: FC
authors: Guo
authors: J
authors: J
authors: Zhang
authors: D
authors: D
authors: Li
authors: B-H
authors: BH
authors: Mo
authors: F
authors: F
authors: Wen
authors: T
authors: T
authors: Liu
authors: Y-T
authors: YT
authors: Liu
authors: Y-S
authors: YS
authors: Wang
authors: Y-Q
authors: YQ
authors: Wei
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D016923:Cell Death; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018274:Electroporation; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D016219:Immunotherapy, Adoptive; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1