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A novel microenvironment regulated system CAR-T (MRS.CAR-T) for immunotherapeutic treatment of esophageal squamous carcinoma.
Wang, Lihong; Wang, Xiaosa; Wu, Yangyang; Wang, Jingjing; Zhou, Wenping; Wang, Jianyao; Guo, Haoran; Zhang, Na; Zhang, Lufang; Hu, Xuanyu; Zhao, Yuanyuan; Miao, Jinxin; Zhang, Zifang; Chard Dunmall, Louisa S; Zhang, Danhua; Lemoine, Nicholas R; Cheng, Zhenguo; Wang, Yaohe.
Afiliación
  • Wang L; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Wang X; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Wu Y; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Wang J; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Zhou W; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Wang J; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Guo H; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Zhang N; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Zhang L; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Hu X; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Zhao Y; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Miao J; Academy of Chinese Medical Sciences, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
  • Zhang Z; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Chard Dunmall LS; Centre for Cancer Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
  • Zhang D; The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
  • Lemoine NR; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China; Centr
  • Cheng Z; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China. Elect
  • Wang Y; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, State Key Laboratory of Esophageal Cancer Prevention & Treatment, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China; Centr
Cancer Lett ; 568: 216303, 2023 08 01.
Article en En | MEDLINE | ID: mdl-37422126
Chimeric antigen receptor T cell immunotherapy has achieved promising therapeutic effects in the treatment of hematological malignancies. However, there are still many obstacles, including on-target off-tumor antigen expression, that prevent successful application to solid tumors. We designed a tumor microenvironment (TME) regulated system chimeric antigen receptor T (MRS.CAR-T) which can only be auto-activated in the solid TME. B7-H3 was selected as the target antigen for esophageal carcinoma. An element comprising a human serum albumin (HSA) binding peptide and a matrix metalloproteases (MMPs) cleavage site was inserted between the 5' terminal signal peptide and single chain fragment variable (scFv) of the CAR skeleton. Upon administration, HSA bound the binding peptide in MRS.B7-H3.CAR-T effectively and promoted proliferation and differentiation into memory cells. MRS.B7-H3.CAR-T was not cytotoxic in normal tissues expressing B7-H3 as the antigen recognition site in the scFv was cloaked by HSA. The anti-tumor function of MRS.B7-H3.CAR-T was recovered once the cleavage site was cleaved by MMPs in the TME. The anti-tumor efficacy associated with MRS.B7-H3.CAR-T cells was improved compared to classic B7-H3.CAR-T cells in vitro and less IFN-γ was released, suggesting a treatment that may induce less extent of cytokine release syndrome-mediated toxicity. In vivo, MRS.B7-H3.CAR-T cells had strong anti-tumor activity and were safe. MRS.CAR-T represents a novel strategy to improve the efficacy and safety of CAR-T therapy in solid tumors.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Receptores Quiméricos de Antígenos / Carcinoma de Células Escamosas de Esófago Idioma: En Revista: Cancer Lett Año: 2023 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Esofágicas / Receptores Quiméricos de Antígenos / Carcinoma de Células Escamosas de Esófago Idioma: En Revista: Cancer Lett Año: 2023 Tipo del documento: Article