A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma

被引:36
作者
Liu, Xiaoqian [1 ]
Zhang, Yuanfeng [1 ]
Li, Kaimin [1 ]
Liu, Yinghui [1 ]
Xu, Junqing [1 ]
Ma, Junjie [1 ]
An, Licai [1 ]
Wang, Hui [1 ]
Chu, Xiaoxia [1 ]
机构
[1] Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Hematol, 20 East Yuhuangding Rd, Yantai 264000, Shandong, Peoples R China
关键词
Lymphoma; Chimeric antigen receptor T cell (CART cell); Programmed cell death-1(PD-1); Clinical trial; NON-HODGKIN-LYMPHOMA; BLOCKADE; THERAPY; COSTIMULATION; COMBINATION; EXPRESSION; CD28;
D O I
10.1016/j.tranon.2021.101085
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 x 10(6)/kg. Grade >= 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.
引用
收藏
页数:8
相关论文
共 37 条
[1]   Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma [J].
Cao, Yaqing ;
Lu, Wenyi ;
Sun, Rui ;
Jin, Xin ;
Cheng, Lin ;
He, Xiaoyuan ;
Wang, Luqiao ;
Yuan, Ting ;
Lyu, Cuicui ;
Zhao, Mingfeng .
FRONTIERS IN ONCOLOGY, 2019, 9
[2]   How I treat early-relapsing follicular lymphoma [J].
Casulo, Carla ;
Barr, Paul M. .
BLOOD, 2019, 133 (14) :1540-1547
[3]   Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study [J].
Casulo, Carla ;
Byrtek, Michelle ;
Dawson, Keith L. ;
Zhou, Xiaolei ;
Farber, Charles M. ;
Flowers, Christopher R. ;
Hainsworth, John D. ;
Maurer, Matthew J. ;
Cerhan, James R. ;
Link, Brian K. ;
Zelenetz, Andrew D. ;
Friedberg, Jonathan W. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (23) :2516-U55
[4]  
Chen Y.Y. Tong, 2019, J CLIN ONCOL, P37
[5]   Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition [J].
Cherkassky, Leonid ;
Morello, Aurore ;
Villena-Vargas, Jonathan ;
Feng, Yang ;
Dimitrov, Dimiter S. ;
Jones, David R. ;
Sadelain, Michel ;
Adusumilli, Prasad S. .
JOURNAL OF CLINICAL INVESTIGATION, 2016, 126 (08) :3130-3144
[6]   Revised response criteria for malignant lymphoma [J].
Cheson, Bruce D. ;
Pfistner, Beate ;
Juweid, Malik E. ;
Gascoyne, Randy D. ;
Specht, Lena ;
Horning, Sandra J. ;
Coiffier, Bertrand ;
Fisher, Richard I. ;
Hagenbeek, Anton ;
Zucca, Emanuele ;
Rosen, Steven T. ;
Stroobants, Sigrid ;
Lister, T. Andrew ;
Hoppe, Richard T. ;
Dreyling, Martin ;
Tobinai, Kensei ;
Vose, Julie M. ;
Connors, Joseph M. ;
Federico, Massimo ;
Diehl, Volker .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586
[7]   Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification [J].
Cheson, Bruce D. ;
Fisher, Richard I. ;
Barrington, Sally F. ;
Cavalli, Franco ;
Schwartz, Lawrence H. ;
Zucca, Emanuele ;
Lister, T. Andrew .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :3059-+
[8]   Sequential Anti-CD19 Directed Chimeric Antigen Receptor Modified T-Cell Therapy (CART19) and PD-1 Blockade with Pembrolizumab in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas [J].
Chong, Elise A. ;
Svoboda, Jakub ;
Nasta, Sunita Dwivedy ;
Landsburg, Daniel J. ;
Winchell, Nicole ;
Napier, Ellen ;
Mato, Anthony R. ;
Melenhorst, J. Joseph ;
Ruella, Marco ;
Lacey, Simon F. ;
June, Carl H. ;
Schuster, Stephen J. .
BLOOD, 2018, 132
[9]   PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR [J].
Chong, Elise A. ;
Melenhorst, J. Joseph ;
Lacey, Simon F. ;
Ambrose, David E. ;
Gonzalez, Vanessa ;
Levine, Bruce L. ;
June, Carl H. ;
Schuster, Stephen J. .
BLOOD, 2017, 129 (08) :1039-1041
[10]  
Dong HD, 1999, NAT MED, V5, P1365