The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer

doi:10.20892/j.issn.2095-3941.2023.0033

科研成果详情

题名	The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer
作者	Wang, Xiaohui 1,2; Qiu, Wei3; Liu, Haoyu 1; He, Min 2; He, Wei 1; Li, Zhan 2; Wu, Zhiqiang 4; Xu, Xiang 2; Chen, Ping 1
发表日期	2023-09-15
发表期刊	Cancer biology & medicine 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	CAR133 CBLB502 TLR5 agonist colorectal cancer endogenous immune response
其他关键词	CHIMERIC ANTIGEN RECEPTOR ; NATURAL-KILLER-CELLS ; T-CELLS ; TUMOR-GROWTH ; FLAGELLIN ; EFFICACY ; TOLL-LIKE-RECEPTOR-5 ; IMMUNOTHERAPY ; ACTIVATION ; ENTOLIMOD
摘要	CAR-T/NK cells have had limited success in the treatment of solid tumors, such as colorectal cancer (CRC), in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response. This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells., {AbstractText=Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines, respectively. Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells (CAR133-i502-NK92). The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release, the RTCA assay, and the degranulation test, as well as measuring tumor bioluminescence signal intensity in mice xenografts.}, {AbstractText=We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation (9.0 × 104 cells vs. 7.0 × 104 cells) and specific anti-tumor activities in vitro and in a xenogeneic mouse model, and were well-tolerated. Notably, CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells. Furthermore, in hCD133+/hCD133- mixed cancer xenograft models, CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts (n = 5, P = 0.0297). Greater T-cell infiltration was associated with greater anti-tumor potency (P < 0.0001).}, Armed with a CBLB502 TLR5 agonist, CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner. This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.
资助项目	Technology Innovation and Application Developnent Key Program of Chongqing[CSTC2021jscx-gksb-N0026];National Natural Science Foundation of China[31540016];Basic Research and Frontier Exploration Projects of Chongqing[cstc2018jcyjAX0075];Subsidy Fund for the Development of National Silk in Chongqing[CQ2018JSCE05]
出版者	CHINA ANTI-CANCER ASSOC
ISSN	2095-3941
卷号	20 期号:9 页码:662-681
DOI	10.20892/j.issn.2095-3941.2023.0033
页数	20
WOS类目	Oncology ; Medicine, Research & Experimental
WOS研究方向	Oncology ; Research & Experimental Medicine
WOS记录号	WOS:001074547700001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-09
URL	查看原文
Pubmed记录号	37731205
Scopus记录号	2-s2.0-85173269530
通讯作者地址	[Xu, Xiang]Department of Stem Cell & Regenerative Medicine,State Key Laboratory of Trauma,Burn and Combined Injury,Daping Hospital,Army Medical University,Chongqing,400042,China ; [Chen, Ping]College of Biotechnology,Southwest University,Chongqing,400715,China
scopus学科分类	Oncology;Cancer Research
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182972
专题	附属第一医院_皮肤科
通讯作者	Xu, Xiang; Chen, Ping
作者单位	1.College of Biotechnology,Southwest University,Chongqing,400715,China; 2.Department of Stem Cell & Regenerative Medicine,State Key Laboratory of Trauma,Burn and Combined Injury,Daping Hospital,Army Medical University,Chongqing,400042,China; 3.Department of Dermatology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China; 4.Department of Biotherapeutics,The First Medical Center,Chinese PLA General Hospital,Beijing,100038,China
推荐引用方式 GB/T 7714	Wang, Xiaohui,Qiu, Wei,Liu, Haoyu,et al. The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer[J]. Cancer biology & medicine,2023,20(9):662-681.
APA	Wang, Xiaohui., Qiu, Wei., Liu, Haoyu., He, Min., He, Wei., ... & Chen, Ping. (2023). The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer. Cancer biology & medicine, 20(9), 662-681.
MLA	Wang, Xiaohui,et al."The inducible secreting TLR5 agonist, CBLB502, enhances the anti-tumor activity of CAR133-NK92 cells in colorectal cancer".Cancer biology & medicine 20.9(2023):662-681.