Phase I Clinical Trial of CD19 CAR-T Cells Expressing CXCR5 Protein for the Treatment of Relapsed or Refractory B-cell Lymphoma.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-09-27 DOI:10.2174/0115680096304530240816111936

Jiaxi Wang, Yirong Jiang, Min Luo, Wenyi Lu, Jixiang He, Meng Zhang, Zhuoxin Yao, Xin Jin, Xia Xiao, Jianhang Chen, Guangchao Li, Wen Ding, Jie Zhou, Zhiyin Zhang, Mingfeng Zhao

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引用次数: 0

Abstract

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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表达 CXCR5 蛋白的 CD19 CAR-T 细胞治疗复发性或难治性 B 细胞淋巴瘤的 I 期临床试验。

背景：CD19 CAR-T 细胞很难进入实体瘤，这也是其治疗淋巴瘤疗效不佳的原因之一。淋巴结中胚层细胞分泌的趋化因子 CXCL13 可诱导 B 淋巴细胞和 T 淋巴细胞归巢，而 B 淋巴细胞和 T 淋巴细胞均表达其受体 CXCR5。临床前试验表明，CD19 CAR-T细胞表达CXCR5可增加其向肿瘤微环境的迁移，并增强其抗肿瘤功能：方法：我们设计了表达第二种受体CXCR5的CD19 CAR-T细胞。然后，我们进行了一项I期临床试验，评估CXCR5 CD19 CAR-T细胞治疗复发或难治性（R/R）B细胞淋巴瘤的安全性和有效性：我们招募了10名接受CXCR5 CD19 CAR-T细胞治疗的R/R B细胞淋巴瘤患者。客观反应率为80%，完全反应率为50%。中位随访时间为15.48个月（3.4-22.3个月），中位无进展生存期（PFS）为8.15个月（1.5-22.33个月）。一名患者在输注 CAR-T 细胞后 1.5 个月（PR 时）接受了 ASCT。1级和2级细胞因子释放综合征（CRS）的发生率分别为70%和20%。没有患者出现3级或3级以上的CRS、神经毒性或输注相关剂量毒性：结论：本研究的结果表明，CXCR5 CD19 CAR-T细胞应在更广泛的患者群体中进行试验研究：试验注册于 www.chictr.org.cn，注册号分别为 ChiCTR2100052677 和 ChiCTR1900028692。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464