Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma

Journal of Hematology & Oncology

Research

Jing Wang¹  Qi Chang²  Cheng Liu²  Fen Zhou³  Jia Xu⁴  Jianghua Wu⁴  Yinqiang Zhang⁴  Danying Liao⁴  Qiuzhe Wei⁴  Mengyi Du⁴  Huiwen Jiang⁴  Cong Lu⁴  Heng Mei⁴  Jun Deng⁴  Yu Hu⁴  Lin Liu⁴  Chenggong Li⁴  Haiming Kou⁴  Sha Ke⁴  Wenjing Luo⁴  Lu Tang⁴ 

[1] Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Eureka Therapeutics, Inc, 94608, Emeryville, CA, USA;Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, 430022, Wuhan, China;Department of Pediatrics, Union Hospital, Tongji Medical College,, Huazhong University of Science and Technology, 430022, Wuhan, China;Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, 430022, Wuhan, Hubei, China;Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, 430022, Wuhan, China;

关键词: γ/δ TCR-T cells;    DLBCL;    Primary CNS lymphoma;    Relapsed or refractory;    Cellular immunotherapy;   

DOI  :  10.1186/s13045-023-01402-y

 received in 2022-11-13, accepted in 2023-01-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundT cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer.MethodsWe previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial.ResultsET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion.ConclusionsCD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients.Trial registration: NCT04014894.

【 授权许可】

CC BY   
© The Author(s) 2023

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