Chimeric antigen receptor T-cells for B-cell malignancies. 2017

Eben I Lichtman, and Gianpietro Dotti
Department of Medicine, University of North Carolina, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC. Electronic address: eben.lichtman@unchealth.unc.edu.

The adoptive transfer of T-lymphocytes modified to express chimeric antigen receptors (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies. This has led to a rapid expansion in the number of clinical trials over the past several years. Although CD19-specific CAR-Ts are the most extensively evaluated, CAR-Ts specific for other B-cell-associated targets have also shown promise. However, despite this success, toxicities associated with CAR-T administration remain a significant concern. There continues to be substantial heterogeneity among CAR-T products, and differences in both CAR designs and CAR-T production strategies can substantially affect clinical outcomes. Ongoing clinical studies will further elucidate these differences and many other innovative approaches are being evaluated at the preclinical level. In this review, we will discuss the background and rationale for the use of CAR-Ts, provide an overview of advances in the field, and examine the application of CAR-Ts to the treatment of B-cell malignancies, including a summary of clinical trials published to date.

UI MeSH Term Description Entries
D011946 Receptors, Antigen Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens. Antigen Receptors,Antigen Receptor,Receptor, Antigen
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D015448 Leukemia, B-Cell A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood. B-Cell Leukemia,B-Lymphocytic Leukemia,Leukemia, Lymphocytic, B-Cell,Lymphocytic Leukemia, B-Cell,Leukemia, Lymphocytic, B Cell,B Cell Leukemia,B Lymphocytic Leukemia,B-Cell Leukemias,B-Cell Lymphocytic Leukemia,B-Cell Lymphocytic Leukemias,B-Lymphocytic Leukemias,Leukemia, B Cell,Leukemia, B-Cell Lymphocytic,Leukemia, B-Lymphocytic,Leukemias, B-Cell,Leukemias, B-Cell Lymphocytic,Leukemias, B-Lymphocytic,Lymphocytic Leukemia, B Cell,Lymphocytic Leukemias, B-Cell
D016219 Immunotherapy, Adoptive Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314) Adoptive Cellular Immunotherapy,Adoptive Immunotherapy,CAR T-Cell Therapy,Cellular Immunotherapy, Adoptive,Chimeric Antigen Receptor Therapy,Immunotherapy, Adoptive Cellular,Adoptive Cellular Immunotherapies,Adoptive Immunotherapies,CAR T Cell Therapy,CAR T-Cell Therapies,Cellular Immunotherapies, Adoptive,Immunotherapies, Adoptive,Immunotherapies, Adoptive Cellular,T-Cell Therapies, CAR,T-Cell Therapy, CAR,Therapies, CAR T-Cell,Therapy, CAR T-Cell
D016393 Lymphoma, B-Cell A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes. B-Cell Lymphoma,B Cell Lymphoma,B-Cell Lymphomas,Lymphoma, B Cell,Lymphomas, B-Cell

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