针对 B 细胞淋巴瘤的嵌合抗原受体 T 细胞治疗的 CD79b 靶点。
Targeting CD79b for Chimeric Antigen Receptor T-Cell Therapy of B-Cell Lymphomas.
机构信息
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan, 430030, Hubei, China.
Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China.
出版信息
Target Oncol. 2020 Jun;15(3):365-375. doi: 10.1007/s11523-020-00729-7.
BACKGROUND
Although chimeric antigen receptor (CAR) T-cell therapy targeting antigens expressed in refractory and relapsed non-Hodgkin B-cell lymphoma, such as CD19 and CD22, has achieved encouraging clinical effects, some patients fail to attain remission, or relapse after CAR T-cell therapy, which has been ascribed to the loss of the target antigens.
OBJECTIVE
To evaluate CD79b as an alternative target for CAR T-cell B-cell lymphoma therapy.
PATIENT AND METHODS
The expression of CD79b in different B-cell lymphomas was determined. Anti-CD79b CAR T-cells expressing one of two different CARs were generated, and a series of in vitro and in vivo experiments were conducted to assess the CAR T-cell function.
RESULTS
We found that CD79b was extensively expressed on the tumor cells of patients with various types of lymphoma regardless of stage, subtype, and cytogenetic and molecular features. Anti-CD79b CAR T-cells were highly specific and effective for the treatment of B-cell lymphomas.
CONCLUSIONS
Our data indicate that CD79b could be used as a target for CAR T-cell therapy of B-cell lymphomas, and further clinical development is warranted.
背景
嵌合抗原受体（CAR）T 细胞疗法针对在难治性和复发性非霍奇金 B 细胞淋巴瘤中表达的抗原，如 CD19 和 CD22，已取得令人鼓舞的临床效果，但一些患者未能缓解，或在 CAR T 细胞治疗后复发，这归因于靶抗原的丢失。
目的
评估 CD79b 作为 CAR T 细胞治疗 B 细胞淋巴瘤的替代靶标。
患者与方法
测定不同 B 细胞淋巴瘤中 CD79b 的表达。生成表达两种不同 CAR 之一的抗 CD79b CAR T 细胞，并进行一系列体外和体内实验以评估 CAR T 细胞功能。
结果
我们发现 CD79b 在各种类型淋巴瘤患者的肿瘤细胞上广泛表达，无论分期、亚型、细胞遗传学和分子特征如何。抗 CD79b CAR T 细胞对 B 细胞淋巴瘤的治疗具有高度特异性和有效性。
结论
我们的数据表明，CD79b 可作为 CAR T 细胞治疗 B 细胞淋巴瘤的靶标，值得进一步临床开发。
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