title: At the Bench: Chimeric antigen receptor (CAR) T cell therapy for the treatment of B cell malignancies.
abstract: The chimeric antigen receptor (CAR) represents the epitome of cellular engineering and is one of the best examples of rational biologic design of a synthetic molecule. The CAR is a single polypeptide with modular domains, consisting of an antibody-derived targeting moiety, fused in line with T cell-derived signaling domains, allowing for T cell activation upon ligand binding. T cells expressing a CAR are able to eradicate selectively antigen-expressing tumor cells in a MHC-independent fashion. CD19, a tumor-associated antigen (TAA) present on normal B cells, as well as most B cell-derived malignancies, was an early target of this technology. Through years of experimental refinement and preclinical optimization, autologously derived CD19-targeting CAR T cells have been successfully, clinically deployed, resulting in dramatic and durable antitumor responses but not without therapy-associated toxicity. As CD19-targeted CAR T cells continue to show clinical success, work at the bench continues to be undertaken to increase further the efficacy of this therapy, while simultaneously minimizing the risk for treatment-related morbidities. In this review, we cover the history and evolution of CAR technology and its adaptation to targeting CD19. Furthermore, we discuss the future of CAR T cell therapy and the need to ask, as well as answer, critical questions as this treatment modality is being translated to the clinic.
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors: Anthony F O
authors: AF
authors: Daniyan
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA; brentjer@mskcc.org.|Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York, USA; and.|Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors: Renier J
authors: RJ
authors: Brentjens
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D051379:Mice; D058990:Molecular Targeted Therapy; D000072417:Protein Domains; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D057170:Translational Research, Biomedical
chemical_list: D018941:Antigens, CD19; D000951:Antigens, Neoplasm; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies
keywords: CD19; adoptive immunotherapy; cellular engineering; synthetic biology