Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells

• Published in: Cytotherapy (Oxford, England) England), 2016-11, Vol.18 (11), p.1393-1409
• Main Authors: Geyer, Mark B, Brentjens, Renier J
• Format: Article
• Language: English
• Subjects: acute lymphoblastic leukemia; adoptive cellular therapy; Advanced Basic Science; Animals; CAR T cells; chimeric antigen receptors; Clinical Trials as Topic; cytokine release syndrome; Humans; Immunotherapy, Adoptive - methods; Neoplasms - immunology; Neoplasms - therapy; Other; Receptors, Antigen, T-Cell - immunology; T-Lymphocytes - immunology
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2016.07.003

Abstract The past several years have been marked by extraordinary advances in clinical applications of immunotherapy. In particular, adoptive cellular therapy utilizing chimeric antigen receptor (CAR)-modified T cells targeted to CD19 has demonstrated substantial clinical efficacy in children and adults with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and durable clinical benefit in a smaller subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (B-NHL). Early-phase clinical trials are currently assessing CAR T-cell safety and efficacy in additional malignancies. Here, we discuss clinical results from the largest series to date investigating CD19-targeted CAR T cells in B-ALL, CLL, and B-NHL, including discussion of differences in CAR T-cell design and production and treatment approach, as well as clinical efficacy, nature of severe cytokine release syndrome and neurologic toxicities, and CAR T-cell expansion and persistence. We additionally review the current and forthcoming use of CAR T cells in multiple myeloma and several solid tumors and highlight challenges and opportunities afforded by the current state of CAR T-cell therapies, including strategies to overcome inhibitory aspects of the tumor microenvironment and enhance antitumor efficacy.