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Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma.
Li, Chenggong; Zhou, Fen; Wang, Jing; Chang, Qi; Du, Mengyi; Luo, Wenjing; Zhang, Yinqiang; Xu, Jia; Tang, Lu; Jiang, Huiwen; Liu, Lin; Kou, Haiming; Lu, Cong; Liao, Danying; Wu, Jianghua; Wei, Qiuzhe; Ke, Sha; Deng, Jun; Liu, Cheng; Mei, Heng; Hu, Yu.
Afiliação
  • Li C; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Zhou F; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Wang J; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Chang Q; Department of Pediatrics, Union Hospital, Tongji Medical College,, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Du M; Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Luo W; Eureka Therapeutics, Inc, Emeryville, CA, 94608, USA.
  • Zhang Y; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Xu J; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Tang L; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Jiang H; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Liu L; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Kou H; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Lu C; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Liao D; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Wu J; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Wei Q; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Ke S; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Deng J; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Liu C; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
  • Mei H; Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China.
  • Hu Y; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
J Hematol Oncol ; 16(1): 5, 2023 01 21.
Article em En | MEDLINE | ID: mdl-36681817
ABSTRACT

BACKGROUND:

T 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.

METHODS:

We 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.

RESULTS:

ET019003 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.

CONCLUSIONS:

CD19-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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma não Hodgkin / Linfoma Difuso de Grandes Células B Limite: Humans Idioma: En Revista: J Hematol Oncol Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma não Hodgkin / Linfoma Difuso de Grandes Células B Limite: Humans Idioma: En Revista: J Hematol Oncol Ano de publicação: 2023 Tipo de documento: Article