title: CD19 chimeric antigen receptor T cell therapy for haematological malignancies.
abstract: T cells can be redirected to recognize tumour antigens by genetic modification to express a chimeric antigen receptor (CAR). These consist of antibody-derived antigen-binding regions linked to T cell signalling elements. CD19 is an ideal target because it is expressed on most B cell malignancies as well as normal B cells but not on other cell types, restricting any 'on target, off tumour' toxicity to B cell depletion. Recent clinical studies involving CD19 CAR-directed T cells have shown unprecedented responses in a range of B cell malignancies, even in patients with chemorefractory relapse. Durable responses have been achieved, although the persistence of modified T cells may be limited. This therapy is not without toxicity, however. Cytokine release syndrome and neurotoxicity appear to be frequent but are treatable and reversible. CAR T cell therapy holds the promise of a tailored cellular therapy, which can form memory and be adapted to the tumour microenvironment. This review will provide a perspective on the currently available data, as well as on future developments in the field.
authors.affiliation: Molecular and Cellular Immunology Unit, Institute of Child Health, University College London, London, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Ghorashian
authors.forename: Martin
authors.initials: M
authors.lastname: Pule
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
mesh_terms: D000818:Animals; D018941:Antigens, CD19; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018014:Gene Transfer Techniques; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: T lymphocytes; cellular therapies; gene transfer; immunotherapy