Shengnan Ding1,2, Xia Mao1,2, Yang Cao1,2, Na Wang1,2, Hao Xu3,4, Jianfeng Zhou5,6. 1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan, 430030, Hubei, China. 2. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China. 3. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan, 430030, Hubei, China. zyxuhao@163.com. 4. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China. zyxuhao@163.com. 5. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Wuhan, 430030, Hubei, China. jfzhou@tjh.tjmu.edu.cn. 6. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China. jfzhou@tjh.tjmu.edu.cn.
Abstract
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.
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-CD79bCAR 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-CD79bCAR 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.