title: TCRγ4δ1-engineered αβT cells exhibit effective antitumor activity.
abstract: T cell engineering with T cell receptors (TCRs) specific for tumors plays an important role in adoptive T-cell transfer (ATC) therapy for cancer. Here, we present a novel strategy to redirect peripheral blood-derived αβT cells against tumors via TCRγ4δ1 gene transduction. The broad-spectrum anti-tumor activity of TCRδ1 cells in innate immunity is dependent on CDR3δ1. TCRγ4δ1-engineered αβT cells were prepared by lentiviral transduction and characterized by analyzing in vitro and in vivo cytotoxicity to tumors, ability of proliferation and cytokine production, and their potential role in autoimmunity. Results show TCRγ4δ1 genes were transduced to approximately 36% of polyclonal αβT cells. TCRγ4δ1-engineered αβT cells exhibited an effective in-vitro TCRγδ-dependent cytotoxicity against various tumor cells via the perforin-granzyme pathway. They also showed a strong proliferative capacity and robust cytokine production. TCRγ4δ1-engineered αβT cells neither expressed mixed TCR dimers nor bound/killed normal cells in vitro. More importantly, adoptive transfer of TCRγ4δ1-engineered αβT cells into nude mice bearing a human HepG2 cell line significantly suppressed tumor growth. Our results demonstrate a novel role for TCRγ4δ1 in gene therapy and ATC for cancer.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.|State Key Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Kangxia
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.|State Key Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.|State Key Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.|State Key Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Lianxian
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.|State Key Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.|State Key Laboratory of Medical Molecular Biology, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
keywords: carcinoma; cell death; gene transfer/gene therapy; immunology; molecular biology; tumor suppressor