title: Using gene therapy to manipulate the immune system in the fight against B-cell leukemias.
abstract: BACKGROUND
  Over 20 years ago, chimeric antigen receptors (CARs) were created to endow T cells with new antigen-specificity and create a therapy that could eradicate cancer and provide life-long protection against recurrence. Steady progress has led to significant improvements with CAR design and CAR T-cell production, allowing evaluation of CAR T cells in patients. The initial trials have targeted CD19, which is expressed on normal and malignant B cells.
  
  
  METHODS
  We review data from trials for patients with chronic lymphocytic leukemia (CLL) and B-cell acute lymphoblastic leukemia (B-ALL). In addition, we discuss the on-target toxicities, B-cell aplasia and cytokine release syndrome (CRS), which is uniquely associated with T-cell immunotherapies.
  
  
  CONCLUSIONS
  We compare the results when targeting the same antigen in CLL or B-ALL and speculate on reasons for outcome differences and future directions to enhance outcomes. Furthermore, the dramatic results targeting B-ALL require further analysis in Phase II trials, and we discuss important components of these future trials. We also suggest a management scheme for CRS. The next several years will be critical and may lead to the first clinical indication of a gene-engineered cell therapy for cancer.
authors: University of Chicago School of Medicine , Chicago, IL , USA.
authors: Diana C G
authors: DC
authors: Bouhassira
authors: Joshua J
authors: JJ
authors: Thompson
authors: Marco L
authors: ML
authors: Davila
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D011946:Receptors, Antigen
keywords: B-cell acute lymphoblastic leukemia; adoptive T-cell therapy; chimeric antigen receptors; chronic lymphocytic leukemia; gene therapy; immunotherapy