TY - JOUR
T1 - 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
AU - Liu, Hui
AU - Lei, Wen
AU - Zhang, Chaoting
AU - Yang, Chunmei
AU - Wei, Juying
AU - Guo, Qunyi
AU - Guo, Xiaojun
AU - Chen, Zhilu
AU - Lu, Ying
AU - Young, Ken H.
AU - Lu, Zheming
AU - Qian, Wenbin
N1 - Funding Information:
The research was supported by National Natural Science Foundation of China (grant Nos. 81830006, 81670178, and 81800188) and funds from Science Technology Department of Zhejiang Province (grant No. 2018C03016-1).
Publisher Copyright:
2020 American Association for Cancer Research.
PY - 2021/1/15
Y1 - 2021/1/15
N2 - 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. Patients and Methods: 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 Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1þ 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-L1þ B-cell lymphoma cells in vitro and in vivo relative to the prototype, CD19-CAR T cells. Among 17 adult patients with R/R lymphoma who received the CAR T therapy, 10 patients had objective response (58.8%), including seven 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 neurologic 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-L1þ large B-cell lymphoma.
AB - 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. Patients and Methods: 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 Ib study to evaluate safety and efficacy of CD19-PD-1/CD28-CAR T cells in the treatment of PD-L1þ 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-L1þ B-cell lymphoma cells in vitro and in vivo relative to the prototype, CD19-CAR T cells. Among 17 adult patients with R/R lymphoma who received the CAR T therapy, 10 patients had objective response (58.8%), including seven 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 neurologic 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-L1þ large B-cell lymphoma.
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U2 - 10.1158/1078-0432.CCR-20-1457
DO - 10.1158/1078-0432.CCR-20-1457
M3 - Article
C2 - 33028589
AN - SCOPUS:85100274484
SN - 1078-0432
VL - 27
SP - 473
EP - 484
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2
ER -