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2000
Volume 25, Issue 9
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

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 stromal 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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Phase I Clinical Trial of CD19 CAR-T Cells Expressing CXCR5 Protein for the Treatment of Relapsed or Refractory B-cell Lymphoma
Curr. Cancer Drug Targets< 25, 1170 (2025); https://doi.org/10.2174/0115680096304530240816111936
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  • Article Type:     Research Article
Keyword(s): CD19 CAR-T; chemokines; CXCL13-CXCR5; cytokine; immunity therapy; Lymphoma

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