CXCR5 guides migration and tumor eradication of anti-EGFR chimeric antigen receptor T cells

Molecular Therapy: Oncolytics

Zheping Han¹  Lingyu Qin²  Yanfang Zheng²  Jintao Guo³  Guangchao Li³  Wenjun Mo³  Wen Ding³  Min Luo³ 

[1] Department of Laboratory Medicine, Central Hospital of Panyu District, Guangzhou, Guangdong Province, China;Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China;Guangzhou Bio-gene Technology Co., Ltd., Guangzhou, Guangdong Province, China;

关键词: CXCR5;    CXCL13;    CAR-T cells;    lung cancer;    immunotherapy;    chemokine;   

DOI  :  

来源: DOAJ

【 摘 要 】

The efficacy of chimeric antigen receptor (CAR) T is still not optimal for solid tumors, partly due to the lack of T cell infiltration to the tumor site. One promising strategy is to guide T cells through tumor-specific chemokines, provided that the matching chemokine receptors are expressed on T cells. Previous reports showed that, for non-small cell lung cancer (NSCLC) patients, the tumor sites express high levels of chemokine CXCL13, whereas CXCR5, the only receptor for CXCL13, is mainly expressed on B cells and follicle helper T cells. Therefore, we engineered an epidermal growth factor receptor (EGFR) CAR-T cell to express a second receptor CXCR5, to facilitate migration of CAR-T cells to the CXCL13-expressing NSCLC tumors, and to minimize EGFR-CAR-T possible off-tumor, on-target toxicity. We first confirmed CXCL13 expression in NSCLC patient blood and cancer tissues and the absence of CXCR5 expression in normal CD3 T cells. Next, we demonstrated that EGFR-CXCR5-CAR-T cells have similar killing activity as EGFR-CAR-T with a cytotoxicity assay in vitro. Furthermore, the in vitro Transwell assay and in vivo xenograft tumor mouse model were used to confirm that EGFR-CXCR5-CAR-T exhibits a significant increase in T cell infiltration to CXCL13-expressing tumors and eradicates the CXCL13-expressing tumors more efficiently.

【 授权许可】

Unknown