title: Cancer CARtography: charting out a new approach to cancer immunotherapy.
abstract: Evaluation of: Davila ML, Riviere I, Wang X et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6(224), 224ra25 (2014). Recently, chimeric antigen receptor (CAR) T-cell immunotherapy has entered clinical trials in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. 19-28z CAR T cells express a fusion protein comprised of an anti-CD19 mAb fused with CD28 costimulatory and CD3-zeta-chain signaling domains. The current paper demonstrates that administration of 19-28z CAR T cells in patients with relapsed or refractory B-ALL in a Phase I clinical trial has led to 88% of patients undergoing complete remission. Despite the benefits, CAR T-cell therapy is associated with cytokine release syndrome toxicities. The authors demonstrated criteria to diagnose severe cytokine release syndrome (sCRS) and treated sCRS with either high-dose steroids or with tocilizumab, an IL-6 receptor-specific mAb. Although both alleviated sCRS, steroid treatment negated the beneficial effects of CAR T-cell therapy, whereas tocilizumab did not. Taken together, CAR T-cell immunotherapy can be used as a safe and effective approach against tumors with known tumor-associated antigens.
authors.affiliation: Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jaina M
authors.initials: JM
authors.lastname: Patel
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Dale
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Vartabedian
authors.forename: Paulami
authors.initials: P
authors.lastname: Dey
authors.forename: Periasamy
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D017690:Cell Transplantation; D005260:Female; D006801:Humans; D007167:Immunotherapy; D015448:Leukemia, B-Cell / Q000628:therapy*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*
keywords: CD19; chimeric antigen receptor; cytokine release syndrome