A novel multimeric sCD19-streptavidin fusion protein for functional detection and selective expansion of CD19-targeted CAR-T cells

doi:10.1002/cam4.4657

科研成果详情

题名	A novel multimeric sCD19-streptavidin fusion protein for functional detection and selective expansion of CD19-targeted CAR-T cells
作者	Lian, Hui 1,2; Jiang, Jinhong3; Wang, Yao 2; Yu, Xiaoxiao 2; Zheng, Rong 2; Long, Jing 2; Zhou, Mengjie 2; Zhou, Shirong 2; Wei, Cheng2; Zhao, Ai 4; Gao, Jimin2,5
发表日期	2022-08
发表期刊	CANCER MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	CAR-T cells CD19 fusion protein streptavidin
其他关键词	MONOMERIC STREPTAVIDIN ; RECEPTOR ; ANTIGEN ; ACTIVATION ; LYMPHOCYTES ; DESIGN ; PURIFICATION ; STIMULATION ; STABILITY ; MOLECULES
摘要	Background CARs are engineered receptors comprising an immunoglobulin single-chain variable fragment (scFv) that identifies and binds to the target antigen, a transmembrane domain, and an intracellular T-cell signaling domain. CD19 is a B lineage-specific transmembrane glycoprotein and is expressed in more than 95% of B-cell malignancies. Streptavidin (SA) is a homo-tetrameric protein derived from Streptomyces avidinii, which can bind four biotin molecules with an extremely high affinity at a Kd value of 10(-15) M. Aims The aim of the study is to generate a novel soluble multimeric fusion protein, sCD19-streptavidin (sCD19-SA) for functional detection and selective expansion of CD19-targeted CAR-T cells. Methods The fusion proteins CD19-SA was expressed in CHO cells and purified by use of Ni-nitrilotriacetic acid agarose beads. Results A novel fusion protein (sCD19-SA) was generated, consisting of the extracellular domain of human CD19 and the core region of SA, and could be used to functionally detect CD19-targeted CAR-T cells. Furthermore, this protein was demonstrated to form multimers to activate CAR-T cells to induce their selective expansion. Importantly, sCD19-SA-stimulated CD19-targeted CAR-T cells could improve antitumor effects in vivo. Conclusions Our study has highlighted the potential of utilizing antigen-SA fusion proteins such as sCD19-SA for CAR-T therapy for the functional detection of CAR expression and selective expansion of CAR-T cells.
资助项目	Scientific Research Fund of the National Health Commission of PR China [WKJ-ZJ-1928]; Guangdong Provincial Natural Science Foundation [2019A1515110831]; Wenzhou Municipal Research Program [ZS2017014, 2018ZY001]; Shandong Provincial Key RD programs [2021CXGC011102]; Construction Fund of Key Medical Disciplines of Hangzhou [OO20200055]
出版者	WILEY
出版地	HOBOKEN
ISSN	2045-7634
卷号	11 期号:15 页码:2978-2989
DOI	10.1002/cam4.4657
页数	12
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000800496700001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	35621033
SCOPUSEID	2-s2.0-85130695437
通讯作者地址	[Wei, Cheng]Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Gao, Jimin]Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Zhao, Ai]Department of Geriatric,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Zhejiang,Hangzhou,China
Scopus学科分类	Oncology;Radiology, Nuclear Medicine and Imaging;Cancer Research
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/147987
专题	检验医学院（生命科学学院、生物学实验教学中心）_模式生物技术与应用重点实验室温州医科大学
通讯作者	Wei, Cheng; Zhao, Ai; Gao, Jimin
作者单位	1.The First People's Hospital of Linping District,Zhejiang,Hangzhou,China; 2.Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Department of Hematology,Lishui People's Hospital,Sixth Affiliated Hospital of Wenzhou Medical University,Zhejiang,Lishui,China; 4.Department of Geriatric,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Zhejiang,Hangzhou,China; 5.Zhejiang Qixin Biotech,Wenzhou,China
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）_模式生物技术与应用重点实验室
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）_模式生物技术与应用重点实验室
推荐引用方式 GB/T 7714	Lian, Hui,Jiang, Jinhong,Wang, Yao,et al. A novel multimeric sCD19-streptavidin fusion protein for functional detection and selective expansion of CD19-targeted CAR-T cells[J]. CANCER MEDICINE,2022,11(15):2978-2989.
APA	Lian, Hui., Jiang, Jinhong., Wang, Yao., Yu, Xiaoxiao., Zheng, Rong., ... & Gao, Jimin. (2022). A novel multimeric sCD19-streptavidin fusion protein for functional detection and selective expansion of CD19-targeted CAR-T cells. CANCER MEDICINE, 11(15), 2978-2989.
MLA	Lian, Hui,et al."A novel multimeric sCD19-streptavidin fusion protein for functional detection and selective expansion of CD19-targeted CAR-T cells".CANCER MEDICINE 11.15(2022):2978-2989.