Jain Michael D, Bachmeier Christina A, Phuoc Vania H, Chavez Julio C
Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA.
Department of Oncologic Sciences, University of South Florida, Tampa, FL, USA.
Ther Clin Risk Manag. 2018 May 31;14:1007-1017. doi: 10.2147/TCRM.S145039. eCollection 2018.
Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis.
过继性T细胞免疫疗法是一个快速发展的领域，正在改变临床癌症治疗的模式。阿基仑赛（axi-cel）是一种抗CD19嵌合抗原受体T细胞疗法，最初由美国国立癌症研究所研发，最近已获得美国食品药品监督管理局的商业批准，用于治疗复发或难治性侵袭性非霍奇金淋巴瘤，包括弥漫性大B细胞淋巴瘤及其变体。ZUMA-1 I期和II期临床试验构成了美国食品药品监督管理局批准该产品的基础，我们将讨论这些临床试验的细节以及阿基仑赛的药理学。此外，我们还回顾了细胞因子释放综合征和神经毒性这两种CD19嵌合抗原受体T细胞特异性毒性，它们仍然是安全应用这种重要疗法治疗预后不良的侵袭性B细胞淋巴瘤的挑战。
