title: Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game changer for adoptive T cell cancer immunotherapy.
abstract: Excitement is growing for therapies that harness the power of patients' immune systems to combat their diseases. One approach to immunotherapy involves engineering patients' own T cells to express a chimeric antigen receptor (CAR) to treat advanced cancers, particularly those refractory to conventional therapeutic agents. Although these engineered immune cells have made remarkable strides in the treatment of patients with certain hematologic malignancies, success with solid tumors has been limited, probably due to immunosuppressive mechanisms in the tumor niche. In nearly all studies to date, T cells bearing αβ receptors have been used to generate CAR T cells. In this review, we highlight biological characteristics of γδ T cells that are distinct from those of αβ T cells, including homing to epithelial and mucosal tissues and unique functions such as direct antigen recognition, lack of alloreactivity, and ability to present antigens. We offer our perspective that these features make γδ T cells promising for use in cellular therapy against several types of solid tumors, including melanoma and gastrointestinal cancers. Engineered γδ T cells should be considered as a new platform for adoptive T cell cancer therapy for mucosal tumors.
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Mirzaei
authors.affiliation: Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Mirzaei
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Hajatij@tums.ac.ir.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Hadjati
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: tillb@fredhutch.org.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Till
mesh_terms: D000818:Animals; D019676:Genes, T-Cell Receptor delta; D019675:Genes, T-Cell Receptor gamma; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D059016:Tumor Microenvironment
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D011993:Recombinant Fusion Proteins
keywords: Cancer therapy; Chimeric antigen receptor; γδ T cells