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一种新型的显性负性PD-1武装抗CD19嵌合抗原受体T细胞对难治性/复发性B细胞淋巴瘤安全有效。

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma.

作者信息

Liu Xiaoqian, Zhang Yuanfeng, Li Kaimin, Liu Yinghui, Xu Junqing, Ma Junjie, An Licai, Wang Hui, Chu Xiaoxia

机构信息

Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong Province, China.

Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong Province, China.

出版信息

Transl Oncol. 2021 Jul;14(7):101085. doi: 10.1016/j.tranon.2021.101085. Epub 2021 Apr 1.

Abstract

Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 × 10/kg. Grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.

摘要

接受过现有抗CD19嵌合抗原受体(CAR)T细胞治疗的难治性/复发性B细胞淋巴瘤患者可能仍会经历较短的缓解期。在本研究中,我们评估了一种新型显性负性程序性细胞死亡蛋白1(PD-1)增强型抗CD19 CAR T细胞的安全性和疗效。共有9例患者(包括4例弥漫性大B细胞淋巴瘤、2例转化型滤泡性淋巴瘤和3例滤泡性淋巴瘤)接受了剂量超过1×10/kg的新型CAR T细胞输注。分别有11.1%(n=1/9)和11.1%(n=1/9)的患者出现≥3级细胞因子释放综合征(CRS)和神经毒性。总缓解率(ORR)为77.8%(n=7/9),完全缓解(CR)率为55.6%(n=5/9)。2例患者持续完全缓解(均超过20个月)。在持续完全缓解的患者中,CAR T细胞在输注后扩增,并在12个月以上仍可检测到。这种新型CD19-CAR T细胞对难治性/复发性B细胞淋巴瘤患者安全有效,可实现持久缓解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d6b/8050776/4179ed3bedbf/gr1.jpg

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