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Mesothelin CAR-T cells secreting PD-L1 blocking scFv for pancreatic cancer treatment.
Wang, Yeying; Fang, Xiaoyan; Li, Minghao; Ye, Jing; Zhao, Shimin; Yu, Lei; Wang, Jing; Wang, Yiting; Yan, Zhiqiang.
Afiliación
  • Wang Y; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China; Medical Frontier Innovation Research Center, The First
  • Fang X; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China.
  • Li M; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China.
  • Ye J; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China.
  • Zhao S; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China.
  • Yu L; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China.
  • Wang J; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China.
  • Wang Y; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China. Electronic address: ytwang@nbic.ecnu.edu.cn.
  • Yan Z; Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P R China. Electronic address: zqyan@sat.ecnu.edu.cn.
Cancer Genet ; 268-269: 103-110, 2022 11.
Article en En | MEDLINE | ID: mdl-36288641
PD-1/PD-L1 pathway caused immunosuppression accounts, at least partly, for the poor therapeutic effect of Chimeric Antigen Receptor T (CAR-T) on solid tumors. In this study, we designed and prepared CAR-T cells that could secrete PD-L1 blocking antibody and target Mesothelin antigen (Sec-MesoCAR-T), to remove the immunosuppressive effect of tumor on CAR-T cells, thereby increasing the therapeutic effect of CAR-T cells on pancreatic cancer. The CAR-T cells that could not secret PD-L1 blocking antibodies (MesoCAR-T) were used as a control. Sec-MesoCAR-T cells showed an enhanced inhibitory effect on BxPC-3 tumor than MesoCAR-T cells in vitro and in vivo. Besides, Sec-MesoCAR-T cells secreted higher level of cytokines including IL-2, IL-6 and IFN-γ in vitro than MesoCAR-T cells. Following injection, there were significantly more CAR-T cells in the peripheral blood of Sec-MesoCAR-T group than that of MesoCAR-T group. This work demonstrated that the PD-L1 antibody secreted by Sec-MesoCAR-T cells relieved the immunosuppressive effect of pancreatic cancer on CAR-T cells and improved the anti-tumor activity of CAR-T cells, which has a good guiding significance for the clinical application of CAR-T cells in treating solid tumors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Antígeno B7-H1 Límite: Humans Idioma: En Revista: Cancer Genet Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Antígeno B7-H1 Límite: Humans Idioma: En Revista: Cancer Genet Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos