title: Chimeric antigen receptor-redirected T cells return to the bench.
abstract: While the clinical progress of chimeric antigen receptor T cell (CAR-T) immunotherapy has garnered attention to the field, our understanding of the biology of these chimeric molecules is still emerging. Our aim within this review is to bring to light the mechanistic understanding of these multi-modular receptors and how these individual components confer particular properties to CAR-Ts. In addition, we will discuss extrinsic factors that can be manipulated to influence CAR-T performance such as choice of cellular population, culturing conditions and additional modifications that enhance their activity particularly in solid tumors. Finally, we will also consider the emerging toxicity associated with CAR-Ts. By breaking apart the CAR and examining the role of each piece, we can build a better functioning cellular vehicle for optimized treatment of cancer patients.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, United States. Electronic address: Claudia.Geldres@mail.nih.gov.
authors.forename: Claudia
authors.initials: C
authors.lastname: Geldres
authors.affiliation: Department of Pediatrics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States. Electronic address: barbar@email.unc.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Savoldo
authors.affiliation: Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States. Electronic address: gdotti@med.unc.edu.
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D018929:Cell Culture Techniques; D015316:Genetic Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
chemical_list: D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Adoptive immunotherapy; Chimeric antigen receptor