Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies

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作者
Yinqiang Zhang
Chenggong Li
Mengyi Du
Huiwen Jiang
Wenjing Luo
Lu Tang
Yun Kang
Jia Xu
Zhuolin Wu
Xindi Wang
Zhongpei Huang
Yanlei Zhang
Di Wu
Alex H. Chang
Yu Hu
Heng Mei
机构
[1] Huazhong University of Science and Technology,Institute of Hematology, Union Hospital, Tongji Medical College
[2] Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease,Clinical Translational Research Center, Shanghai Pulmonary Hospital
[3] Shanghai YaKe Biotechnology Ltd,undefined
[4] Beijing GoBroad Hospital Management Co. Ltd,undefined
[5] Tongji University School of Medicine,undefined
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摘要
Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.
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