title: Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy.
abstract: Chimeric antigen receptors (CAR) are engineered fusion proteins constructed from antigen recognition, signaling, and costimulatory domains that can be expressed in cytotoxic T cells with the purpose of reprograming the T cells to specifically target tumor cells. CAR T-cell therapy uses gene transfer technology to reprogram a patient's own T cells to stably express CARs, thereby combining the specificity of an antibody with the potent cytotoxic and memory functions of a T cell. In early-phase clinical trials, CAR T cells targeting CD19 have resulted in sustained complete responses within a population of otherwise refractory patients with B-cell malignancies and, more specifically, have shown complete response rates of approximately 90% in patients with relapsed or refractory acute lymphoblastic leukemia. Given this clinical efficacy, preclinical development of CAR T-cell therapy for a number of cancer indications has been actively investigated, and the future of the CAR T-cell field is extensive and dynamic. Several approaches to increase the feasibility and safety of CAR T cells are currently being explored, including investigation into the mechanisms regulating the persistence of CAR T cells. In addition, numerous early-phase clinical trials are now investigating CAR T-cell therapy beyond targeting CD19, especially in solid tumors. Trials investigating combinations of CAR T cells with immune checkpoint blockade therapies are now beginning and results are eagerly awaited. This review evaluates several of the ongoing and future directions of CAR T-cell therapy.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts. mvmaus@mgh.harvard.edu cjune@exchange.upenn.edu.
authors.forename: Marcela V
authors.initials: MV
authors.lastname: Maus
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. mvmaus@mgh.harvard.edu cjune@exchange.upenn.edu.
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D006801:Humans; D056747:Immunomodulation; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins
chemical_list: D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins