CXCR5型
医学
细胞因子释放综合征
淋巴瘤
CD19
内科学
CXCL13型
肿瘤科
嵌合抗原受体
癌症研究
T细胞
免疫学
趋化因子受体
趋化因子
抗体
免疫系统
受体
作者
Jiaxi Wang,Yirong Jiang,Min Luo,Wenyi Lu,Jixiang He,Meng Zhang,Zhuoxin Yao,Xin Jin,Xia Xiao,Jianhang Chen,Guangchao Li,Wenyuan Ding,Jie Zhou,Zhiyong Zhang,Mingfeng Zhao
出处
期刊:Current Cancer Drug Targets
[Bentham Science]
日期:2024-09-27
卷期号:24
标识
DOI:10.2174/0115680096304530240816111936
摘要
Background: It is difficult for CD19 CAR-T cells to enter solid tumors, which is one reason for their poor efficacy in lymphoma treatment. The chemokine CXCL13 secreted by stro-mal cells of the lymph nodes induces the homing of B and T lymphocytes, which express its receptor CXCR5. Preclinical trials have shown that the expression of CXCR5 on CD19 CAR-T cells can increase their migration to the tumor microenvironment and enhance their antitumor function. Methods: We engineered the CD19 CAR-T cells to express a second receptor, CXCR5. Then, we conducted a phase I clinical trial to evaluate the safety and efficacy of CXCR5 CD19 CAR-T cells in the treatment of relapsed or refractory (R/R) B-cell lymphoma. Results: We recruited 10 patients with R/R B-cell lymphoma undergoing CXCR5 CD19 CAR-T cell therapy. The objective response rate was 80%, and the complete response rate was 50%. The median follow-up time was 15.48 months (3.4-22.3 months), and the median Progression-Free Survival (PFS) time was 8.15 months (1.5-22.33 months). One patient received ASCT at 1.5 months (at PR) after infusion of CAR-T cells. The incidence of grade 1 and grade 2 Cytokine Release Syndrome (CRS) was 70% and 20%, respectively. No patient experienced grade 3 or higher levels of CRS, neurotoxicity, or infusion-related dose toxicity. Conclusion: The results obtained in this study suggest that CXCR5 CD19 CAR-T cells should be investigated in a trial with broader patient populations. Trial Registration: The trials were registered at www.chictr.org.cn as ChiCTR2100052677 and ChiCTR1900028692.
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