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

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• 作者：Mark B. Geyer¹ ; Renier J. Brentjens¹ ; ² ; ³ ; ^{brentjer@mskcc.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：acute lymphoblastic leukemia ; adoptive cellular therapy ; CAR T cells ; chimeric antigen receptors ; cytokine release syndrome
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：18
• 期：11
• 页码：1393-1409
• 全文大小：507 K

文摘

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.