title: Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies.
abstract: The genetic modification of autologous T cells with chimeric antigen receptors (CARs) represents a breakthrough for gene engineering as a cancer therapy for hematologic malignancies. By targeting the CD19 antigen, we have demonstrated robust and rapid anti-leukemia activity in patients with heavily pre-treated and chemotherapy-refractory B cell acute lymphoblastic leukemia (B-ALL). We demonstrated rapid induction of deep molecular remissions in adults, which has been recently confirmed in a case report involving a child with B-ALL. In contrast to the results when treating B-ALL, outcomes have been more modest in patients with chronic lymphocytic leukemia (CLL) or other non-hodgkin's lymphoma (NHL). We review the clinical trial experience targeting B-ALL and CLL and speculate on the possible reasons for the different outcomes and propose potential optimization to CAR T cell therapy when targeting CLL or other indolent NHL. Lastly, we discuss the pre-clinical development and potential for clinical translation for using CAR T cells against multiple myeloma and acute myeloid leukemia. We highlight the potential risks and benefits by targeting these poor outcome hematologic malignancies.
authors: Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA, davilam@mskcc.org.
authors: Marco L
authors: ML
authors: Davila
authors: Diana C G
authors: DC
authors: Bouhassira
authors: Jae H
authors: JH
authors: Park
authors: Kevin J
authors: KJ
authors: Curran
authors: Eric L
authors: EL
authors: Smith
authors: Hollie J
authors: HJ
authors: Pegram
authors: Renier
authors: R
authors: Brentjens
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D015316:Genetic Therapy; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000628:therapy; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins