Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors

doi:10.1002/anie.202002145

	Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors
	Zhang, Da 1,4; Zheng, Youshi 1; Lin, Ziguo 1; Liu, Xiaolong 1; Li, Juan 2,3,4; Yang, Huanghao 4; Tan, Weihong 2,3
刊名	ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
	2020-05-12
关键词	aptamers immunology natural killer cells PD1 PDL1 checkpoint blockade solid tumors
ISSN号	1433-7851
DOI	10.1002/anie.202002145
通讯作者	Li, Juan(lijuan@fzu.edu.cn) ; Yang, Huanghao(hhyang@fzu.edu.cn)
英文摘要	Herein, we propose an aptamer-equipping strategy to generate specific, universal and permeable (SUPER) NK cells for enhanced immunotherapy in solid tumors. NK cells were chemically equipped with TLS11a aptamer targeting HepG2 cells and PDL1-specific aptamer without genetic alteration. The dual aptamer-equipped NK cells exhibited high specificity to tumor cells, resulting in higher cytokine secretion and apoptosis/necrosis compared to parental or single aptamer-equipped NK cells. Interestingly, dual aptamer-equipped NK cells induced remarkable upregulation of PDL1 expression in HepG2 cells, enhancing checkpoint blockade. Furthermore, in vivo intravital imaging demonstrated high infiltration of aptamer-equipped NK cells into deep tumor region, leading to enhanced therapeutic efficacy in solid tumors. This work offers a straightforward chemical strategy to equip NK cells with aptamers, holding considerable potential for enhanced adoptive immunotherapy in solid tumors.
资助项目	Natural Science Foundation of China[91959102] ; Natural Science Foundation of China[21635002] ; Natural Science Foundation of China[61805041] ; Natural Science Foundation of Fujian Province of China[2017J06004] ; Shanghai Rising-Star Program[19QA1405400] ; Program for Changjiang Scholars and Innovative Research Team in University[IRT15R11]
WOS关键词	CANCER-IMMUNOTHERAPY ; TRANSFER THERAPY ; DNA APTAMER
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000531691900001
资助机构	Natural Science Foundation of China ; Natural Science Foundation of Fujian Province of China ; Shanghai Rising-Star Program ; Program for Changjiang Scholars and Innovative Research Team in University
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/103281]
专题	中国科学院合肥物质科学研究院
通讯作者	Li, Juan; Yang, Huanghao
作者单位	1.Fujian Med Univ, Mengchao Hepatobiliary Hosp, United Innovat Mengchao Hepatobiliary Technol Key, Fuzhou 350025, Peoples R China 2.Univ Chinese Acad Sci, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China 3.Chinese Acad Sci, Inst Canc & Basic Med, Hangzhou 310022, Zhejiang, Peoples R China 4.Fuzhou Univ, MOE Key Lab Analyt Sci Food Safety & Biol, Fujian Prov Key Lab Anal & Detect Technol Food Sa, Coll Chem,State Key Lab Photocatalysis Energy & E, Fuzhou 350116, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Da,Zheng, Youshi,Lin, Ziguo,et al. Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2020.
APA	Zhang, Da.,Zheng, Youshi.,Lin, Ziguo.,Liu, Xiaolong.,Li, Juan.,...&Tan, Weihong.(2020).Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION.
MLA	Zhang, Da,et al."Equipping Natural Killer Cells with Specific Targeting and Checkpoint Blocking Aptamers for Enhanced Adoptive Immunotherapy in Solid Tumors".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020).