Your browser doesn't support javascript.
loading
Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy.
Zhou, Xiuman; Jiao, Ling; Qian, Yuzhen; Dong, Qingyu; Sun, Yixuan; Zheng, Wei V; Zhao, Wenshan; Zhai, Wenjie; Qiu, Lu; Wu, Yahong; Wang, Hongfei; Gao, Yanfeng; Chen, Junhui.
Afiliación
  • Zhou X; Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, China.
  • Jiao L; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Qian Y; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Dong Q; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Sun Y; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Zheng WV; Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, China.
  • Zhao W; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Zhai W; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Qiu L; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Wu Y; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Wang H; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • Gao Y; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China.
  • Chen J; Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518035, China.
Biomolecules ; 11(5)2021 05 10.
Article en En | MEDLINE | ID: mdl-34068552
Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated. Here, an elevated expression of CD47 and PVR was observed in tumor tissues and cell lines analyzed with the GEO datasets and by flow cytometry, respectively. Compounds approved by the FDA were screened with the software MOE by docking to the potential binding pockets of SIRPα and PVR identified with the corresponding structural analysis. The candidate compounds were screened by blocking and MST binding assays. Azelnidipine was found to dual block CD47/SIRPα and TIGIT/PVR pathways by co-targeting SIRPα and PVR. In vitro, azelnidipine could enhance the macrophage phagocytosis when co-cultured with tumor cells. In vivo, azelnidipine alone or combined with irradiation could significantly inhibit the growth of MC38 tumors. Azelnidipine also significantly inhibits the growth of CT26 tumors, by enhancing the infiltration and function of CD8+ T cell in tumor and systematic immune response in the tumor-draining lymph node and spleen in a CD8+ T cell dependent manner. Our research suggests that the anti-hypertensive drug azelnidipine could be repositioned for cancer immunotherapy.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Azetidinocarboxílico / Dihidropiridinas / Regulación Neoplásica de la Expresión Génica / Reposicionamiento de Medicamentos / Inmunoterapia / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Biomolecules Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Azetidinocarboxílico / Dihidropiridinas / Regulación Neoplásica de la Expresión Génica / Reposicionamiento de Medicamentos / Inmunoterapia / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Biomolecules Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza