Phase I clinical trial of CD19 CAR-T cells expressing CXCR5 protein for the treatment of relapsed or refractory B-cell lymphoma

Abstract Background The difficulty of CD19 CAR-T cells entering solid tumors is one of the reasons for its poor efficacy in the treatment of lymphoma.The chemokine CXCL13 secreted by stromal cells of the lymph nodes, induces the homing of B and T lymphocytes who express its receptor CXCR5. Pre-clinical trials have shown that CD19 CAR-T cells expressing CXCR5 could increase its migration to the tumor microenvironment and enhance the anti-tumor function of CD19 CAR-T cells. Methods We generated a novel anti-CD19 CAR-expressing CXCR5 protein. Then, we conducted a phase I clinical trial to evaluate 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 cells therapy. The objective response rate was 80%, complete response rate was 50%. The progression-free survival of these ten patients was 5 months (95% CI 1.02-8.98 months), while the median overall survival was 17.76 months (95% CI 13.54-21.98 months). The incidence of grade 1 and grade 2 cytokine release syndrome (CRS) was 70% and 20%, respectively. No patient experienced grade 3 or higher level of CRS, neurotoxicity and infusion-related dose toxicity. Conclusions In this study, we suggest that the results obtained here can pave the way for CXCR5 CD19 CAR-T cells to be investigated in a trial with broader patient populations. Trial registration The trials were registered at www.chictr.org.cn as ChiCTR2100052677 and ChiCTR1900028692.