Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy
Abstract Background Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor...
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BMC
2025-01-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-025-02132-y |
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| _version_ | 1832571300508336128 |
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| author | Xiangrui Zhang Lihan Zhang Beibei Li Qingchao Wang Peixin Chen Ranran Shi Xiuman Zhou Xiaoshuang Niu Wenjie Zhai Yahong Wu Wenhui Shen Xiaowen Zhou Wenshan Zhao |
| author_facet | Xiangrui Zhang Lihan Zhang Beibei Li Qingchao Wang Peixin Chen Ranran Shi Xiuman Zhou Xiaoshuang Niu Wenjie Zhai Yahong Wu Wenhui Shen Xiaowen Zhou Wenshan Zhao |
| author_sort | Xiangrui Zhang |
| collection | DOAJ |
| description | Abstract Background Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor immune evasion. Therefore, screening of immune checkpoint inhibitors (ICIs) targeting the CD96/PVR pathway will provide promising candidates for tumor immunotherapy. Results In this investigation, we employed MOE software to conduct virtual screening of small molecules from the FDA-approved drug library. Our results demonstrated that Epinastine exhibited high affinity for CD96, thereby effectively disrupting the interaction between CD96 and PVR. In vitro co-culture experiments further revealed that Epinastine effectively restored the ability of Jurkat cells to secrete IL-2. In the MC38 tumor-bearing model, Epinastine significantly enhanced the infiltration of T cells and NK cells into the tumor site and augmented their secretion of IFN-γ, leading to effective suppression of tumor growth. Conclusions Our results demonstrated that the development of small molecule inhibitor Epinastine targeting CD96/PVR pathway, which proposed a promising strategy and drug candidate for cancer immunotherapy. Graphical Abstract |
| format | Article |
| id | doaj-art-4f36fd8080584cc89402ddc1b1a0ea21 |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-4f36fd8080584cc89402ddc1b1a0ea212025-02-02T12:42:40ZengBMCBMC Biology1741-70072025-01-0123111510.1186/s12915-025-02132-yIdentification of Epinastine as CD96/PVR inhibitor for cancer immunotherapyXiangrui Zhang0Lihan Zhang1Beibei Li2Qingchao Wang3Peixin Chen4Ranran Shi5Xiuman Zhou6Xiaoshuang Niu7Wenjie Zhai8Yahong Wu9Wenhui Shen10Xiaowen Zhou11Wenshan Zhao12School of Life Sciences, Zhengzhou UniversityDepartment of Integrated Chinese and Western Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalSchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityDepartment of Basic Medical Sciences, Luohe Medical CollegeSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen UniversitySchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen UniversitySchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityDepartment of Head Neck and Thyroid, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer HospitalSchool of Life Sciences, Zhengzhou UniversitySchool of Life Sciences, Zhengzhou UniversityAbstract Background Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor immune evasion. Therefore, screening of immune checkpoint inhibitors (ICIs) targeting the CD96/PVR pathway will provide promising candidates for tumor immunotherapy. Results In this investigation, we employed MOE software to conduct virtual screening of small molecules from the FDA-approved drug library. Our results demonstrated that Epinastine exhibited high affinity for CD96, thereby effectively disrupting the interaction between CD96 and PVR. In vitro co-culture experiments further revealed that Epinastine effectively restored the ability of Jurkat cells to secrete IL-2. In the MC38 tumor-bearing model, Epinastine significantly enhanced the infiltration of T cells and NK cells into the tumor site and augmented their secretion of IFN-γ, leading to effective suppression of tumor growth. Conclusions Our results demonstrated that the development of small molecule inhibitor Epinastine targeting CD96/PVR pathway, which proposed a promising strategy and drug candidate for cancer immunotherapy. Graphical Abstracthttps://doi.org/10.1186/s12915-025-02132-yCD96PVRImmune checkpoint inhibitorSmall moleculeCancer immunotherapy |
| spellingShingle | Xiangrui Zhang Lihan Zhang Beibei Li Qingchao Wang Peixin Chen Ranran Shi Xiuman Zhou Xiaoshuang Niu Wenjie Zhai Yahong Wu Wenhui Shen Xiaowen Zhou Wenshan Zhao Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy BMC Biology CD96 PVR Immune checkpoint inhibitor Small molecule Cancer immunotherapy |
| title | Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy |
| title_full | Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy |
| title_fullStr | Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy |
| title_full_unstemmed | Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy |
| title_short | Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy |
| title_sort | identification of epinastine as cd96 pvr inhibitor for cancer immunotherapy |
| topic | CD96 PVR Immune checkpoint inhibitor Small molecule Cancer immunotherapy |
| url | https://doi.org/10.1186/s12915-025-02132-y |
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