CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1–positive B-Cell Lymphoma
- 7 October 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 27 (2), 473-484
- https://doi.org/10.1158/1078-0432.ccr-20-1457
Abstract
Purpose: CD19-specific chimeric antigen receptor (CAR)-T cell therapy is effective against refractory or relapsed (R/R) B-cell lymphoma, but the efficacy is hindered by the existence of PD-1/PD-L1 pathway. Experimental Design: Here we generated a novel anti-CD19 CAR expressing PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR). We then conducted a phase 1b study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1+ B-cell lymphoma. Results: We found that CD19-PD-1/CD28-CAR T cells had superior T-cell proliferation, cytokine production, and sequentially, capability of killing PD-L1+ B-cell lymphoma cells in vitro and in vivo relative to the prototype CD19-CAR T cells. Among total of 17 adult patients with R/R lymphoma received the CAR-T therapy, 10 patients had objective response (58.8%), including 7 patients with complete remission (41.2%). At a median follow-up 15 months, median overall survival for all patients was not reached. Remarkably, no severe neurological toxicity or cytokine-release syndrome was observed. Conclusions: This first-in-human study demonstrates the tolerability, safety, and encouraging efficacy of CD19-PD-1/CD28-CART in PD-L1+ large B-cell lymphoma.Funding Information
- National Natural Science Foundation of China (81830006)
- National Natural Science Foundation of China (81670178)
- National Natural Science Foundation of China (81800188)
- Funds of Science Technology Department of Zhejiang Province (2018C03016-1)
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