title: Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors.
abstract: Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a patient with advanced-stage lymphoma treated at the NCI experienced a partial remission of lymphoma and long-term eradication of normal B cells. Additional patients have subsequently obtained long-term remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR T cells. Long-term eradication of normal CD19(+) B cells from patients receiving infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific activity of these T cells. Some patients treated with anti-CD19 CAR T cells have experienced acute adverse effects, which were associated with increased levels of serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early stage of development, the potent antigen-specific activity observed in patients suggests that infusions of anti-CD19 CAR T cells might become a standard therapy for some B-cell malignancies.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. kochendj@mail.nih.gov
authors.forename: James N
authors.initials: JN
authors.lastname: Kochenderfer
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D018274:Electroporation; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012074:Remission Induction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018941:Antigens, CD19; D000970:Antineoplastic Agents; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
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