Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma

doi:10.1038/s41421-023-00625-0

科研成果详情

题名	Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma
作者	Lei, Wen 1,2; Zhao, Ai3,4; Liu, Hui 1,2; Yang, Chunmei 2; Wei, Cheng3; Guo, Shanshan 1; Chen, Zhilu 5; Guo, Qunyi6; Li, Linjie 7; Zhao, Mingzhe 8; Wu, Gongqiang9; Ouyang, Guifang 10; Liu, Ming 11; Zhang, Jinyi11; Gao, Jimin3,12; Qian, Wenbin 1,2
发表日期	2024-01-09
发表期刊	Cell Discovery 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	EXPANSION
摘要	Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 x 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 x 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 x 19 CAR-T with doses ranged from 0.5 x 106-4.0 x 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and >= grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 x 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.
资助项目	National Natural Science Foundation of China (National Science Foundation of China) [81830006, 82170219, 31970841]; National Natural Science Foundation of China [2021C03117]; Science Technology Department of Zhejiang Province
出版者	SPRINGERNATURE
ISSN	2056-5968
EISSN	2056-5968
卷号	10 期号:1
DOI	10.1038/s41421-023-00625-0
页数	14
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:001137777700003
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	38191529
SCOPUSEID	2-s2.0-85191886018
通讯作者地址	[Qian, Wenbin]Department of Hematology,The Second Affiliated Hospital,College of Medicine,Zhejiang University,Zhejiang,Hangzhou,China ; [Gao, Jimin]Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Zhang, Jinyi]Oujiang Laboratory,Zhejiang Lab for Regenerative Medicine,Vision and Brain Health,Eye Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Biochemistry;Molecular Biology;Genetics;Cell Biology
SCOPUS_ID	SCOPUS_ID:85191886018
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/209429
专题	检验医学院（生命科学学院、生物学实验教学中心）眼视光学院（生物医学工程学院）、附属眼视光医院附属台州医院其他_附属东阳医院（东阳市人民医院）其他_附属台州医院（浙江省台州医院）其他_瓯江实验室
通讯作者	Zhang, Jinyi; Gao, Jimin; Qian, Wenbin
作者单位	1.Department of Hematology,The Second Affiliated Hospital,College of Medicine,Zhejiang University,Zhejiang,Hangzhou,China; 2.Institute of Hematology,the First Affiliated Hospital,College of Medicine,Zhejiang University,Zhejiang,Hangzhou,China; 3.Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 4.Department of Geriatrics,Affiliated Hangzhou First People’s Hospital,Westlake University School of Medicine,Zhejiang,Hangzhou,China; 5.Department of Hematology,Tongde Hospital of Zhejiang Province,Zhejiang,Hangzhou,China; 6.Department of Hematology,Taizhou Hospital of Zhejiang Province,Wenzhou Medical University,Zhejiang,Linhai,China; 7.Department of Hematology,Lishui Municipal Central Hospital,Zhejiang,Lishui,China; 8.Department of Hematology,Jinhua Municipal Central Hospital,Zhejiang,Jinhua,China; 9.Department of Hematology,Dongyang People’s Hospital,Wenzhou Medical University,Zhejiang,Dongyang,China; 10.Ningbo Clinical Research Center for Hematological Tumor Diseases,Department of hematology,the First Affiliated Hospital of Ningbo University,Zhejiang,Ningbo,China; 11.Oujiang Laboratory,Zhejiang Lab for Regenerative Medicine,Vision and Brain Health,Eye Hospital,Wenzhou Medical University,Zhejiang,Wenzhou,China; 12.Hangzhou Qilan Biomedical Technology Co.,Ltd,Zhejiang,Hangzhou,China
通讯作者单位	检验医学院（生命科学学院、生物学实验教学中心）; 眼视光学院（生物医学工程学院）、附属眼视光医院; 瓯江实验室
推荐引用方式 GB/T 7714	Lei, Wen,Zhao, Ai,Liu, Hui,et al. Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma[J]. Cell Discovery,2024,10(1).
APA	Lei, Wen., Zhao, Ai., Liu, Hui., Yang, Chunmei., Wei, Cheng., ... & Qian, Wenbin. (2024). Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma. Cell Discovery, 10(1).
MLA	Lei, Wen,et al."Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma".Cell Discovery 10.1(2024).