Division of Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, PR China.
Leuk Lymphoma. 2013 Feb;54(2):255-60. doi: 10.3109/10428194.2012.715350. Epub 2012 Sep 8.
There remain some key questions regarding the adoptive infusion of chimeric antigen receptor (CAR) transduced T-cells in the clinical setting. This article systematically reviews the phase I clinical trials using CARs targeting CD19 in B-lineage malignancies. Twenty-nine patients were enrolled and the 6-month progression free survival for this cohort was 50.0 ± 9.9%. Univariate analysis showed that patients benefited from lymphodepletion before CAR+T-cell infusion and the administration of interleukin-2 (IL-2). Longer-term persistence (≥ 4 weeks) and stronger expansion of CAR+ T-cells in the blood and higher peak serum interferon-γ (IFN-γ) level (≥ 200 pg/mL) were also related to superior outcome. Regarding treatment-related adverse events, the most prominent toxicities were fever, rigors, chills, acute renal failure, hypotension and capillary leak syndrome. In conclusion, anti-CD19 CAR+ T-cells have shown some benefits in patients with B-lineage malignancies and are well tolerated in most patients. Preconditioning and cytokine supplement are required to improve the clinical outcome.
关于嵌合抗原受体(CAR)修饰的 T 细胞过继输注在临床环境中的应用仍存在一些关键问题。本文系统综述了靶向 B 细胞恶性肿瘤 CD19 的 CAR 的 I 期临床试验。共纳入 29 例患者,该队列的 6 个月无进展生存率为 50.0±9.9%。单因素分析显示,患者在接受 CAR+T 细胞输注前接受淋巴细胞耗竭治疗以及白细胞介素-2(IL-2)治疗可获益。CAR+T 细胞在血液中持续时间更长(≥4 周)和扩增更强,以及血清干扰素-γ(IFN-γ)峰值水平更高(≥200pg/mL)也与更好的结果相关。关于治疗相关的不良反应,最突出的毒性是发热、寒战、发冷、急性肾衰竭、低血压和毛细血管渗漏综合征。总之,抗 CD19 CAR+T 细胞在 B 细胞恶性肿瘤患者中显示出一定的益处,并且大多数患者均可耐受。需要预处理和细胞因子补充来改善临床结局。
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