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
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
复制标题
表达 PD-1/CD28 嵌合开关受体的 CD19 特异性 CAR T 细胞对 PD-L1 阳性 B 细胞淋巴瘤患者有效。
DOI：
10.1158/1078-0432.ccr-20-1457
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发表时间：
2021-01-15
影响因子：
11.5
通讯作者：
Qian, Wenbin
中科院分区：
文献类型：
--
作者：
Liu, Hui;Lei, Wen;Qian, Wenbin
目的：cd19特异性嵌合抗原受体（CAR） t细胞治疗对难治性或复发性（R/R） b细胞淋巴瘤有效，但PD-1/PD-L1通路的存在阻碍了疗效。患者和方法：在这里，我们产生了一种新的表达PD-1/CD28嵌合开关受体（CD19-PD-1/CD28- car）的抗cd19 car。然后，我们进行了一项Ib期研究，以评估CD19-PD-1/CD28-CAR - T细胞治疗pd - l1刺状b细胞淋巴瘤的安全性和有效性。结果：我们发现CD19-PD-1/CD28-CAR - T细胞在体外和体内均比原型CD19-CAR - T细胞具有更强的T细胞增殖、细胞因子产生和杀伤pd - l1刺状b细胞淋巴瘤细胞的能力。在接受CAR - T治疗的17例成年R/R淋巴瘤患者中，10例患者客观缓解（58.8%），其中7例患者完全缓解（41.2%）。在中位随访15个月时，所有患者的中位总生存期均未达到。值得注意的是，没有观察到严重的神经毒性或细胞因子释放综合征。结论：这项首次人体研究证明了CD19-PD-1/CD28-CART治疗pd - l1棘大b细胞淋巴瘤的耐受性、安全性和令人鼓舞的疗效。
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-L1thorn 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-L1thorn 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-L1thorn large B-cell lymphoma.