title: CD19-Targeted chimeric antigen receptor-modified T-cell immunotherapy for B-cell malignancies.
abstract: Chimeric antigen receptors (CARs) comprise a tumor-targeting moiety, often in the form of a single chain variable fragment derived from a monoclonal antibody, fused to one or more intracellular T-cell signaling sequences. Lymphodepletion chemotherapy followed by infusion of T cells that are genetically modified to express a CD19-specific CAR is a promising therapy for patients with refractory CD19(+) B-cell malignancies, producing rates of complete remission that are remarkably high in acute lymphoblastic leukemia and encouraging in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Responses are often durable, although additional studies are needed to define the role of CAR-T cell immunotherapy in the context of other treatments. CAR-modified T-cell immunotherapy can be complicated by cytokine release syndrome and neurologic toxicity, which in most cases are manageable and reversible. Here we review recent clinical trial data and discuss issues for the field.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Turtle
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Riddell
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Maloney
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology*; D001402:B-Lymphocytes; D002986:Clinical Trials as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D011948:Receptors, Antigen, T-Cell