Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy
Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid d...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523002940 |
| _version_ | 1827781812697432064 |
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| author | Xiaoshuang Niu Menghan Wu Guodong Li Xiuman Zhou Wenpeng Cao Wenjie Zhai Aijun Wu Xiaowen Zhou Shengzhe Jin Guanyu Chen Yanying Li Jiangfeng Du Yahong Wu Lu Qiu Wenshan Zhao Yanfeng Gao |
| author_facet | Xiaoshuang Niu Menghan Wu Guodong Li Xiuman Zhou Wenpeng Cao Wenjie Zhai Aijun Wu Xiaowen Zhou Shengzhe Jin Guanyu Chen Yanying Li Jiangfeng Du Yahong Wu Lu Qiu Wenshan Zhao Yanfeng Gao |
| author_sort | Xiaoshuang Niu |
| collection | DOAJ |
| description | Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy. |
| first_indexed | 2024-03-11T15:24:13Z |
| format | Article |
| id | doaj.art-6351c959bc1240cab10ee9ff5e5547e1 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-11T15:24:13Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-6351c959bc1240cab10ee9ff5e5547e12023-10-28T05:07:03ZengElsevierActa Pharmaceutica Sinica B2211-38352023-11-01131145114522Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapyXiaoshuang Niu0Menghan Wu1Guodong Li2Xiuman Zhou3Wenpeng Cao4Wenjie Zhai5Aijun Wu6Xiaowen Zhou7Shengzhe Jin8Guanyu Chen9Yanying Li10Jiangfeng Du11Yahong Wu12Lu Qiu13Wenshan Zhao14Yanfeng Gao15School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; International Joint Laboratory for Protein and Peptide Drugs of Henan Province, Zhengzhou University, Zhengzhou 450001, China; Corresponding authors.School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Corresponding authors.Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.http://www.sciencedirect.com/science/article/pii/S2211383523002940Immune checkpointVISTAPSGL-1Phage displayed bio-panningPeptideCancer immunotherapy |
| spellingShingle | Xiaoshuang Niu Menghan Wu Guodong Li Xiuman Zhou Wenpeng Cao Wenjie Zhai Aijun Wu Xiaowen Zhou Shengzhe Jin Guanyu Chen Yanying Li Jiangfeng Du Yahong Wu Lu Qiu Wenshan Zhao Yanfeng Gao Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy Acta Pharmaceutica Sinica B Immune checkpoint VISTA PSGL-1 Phage displayed bio-panning Peptide Cancer immunotherapy |
| title | Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy |
| title_full | Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy |
| title_fullStr | Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy |
| title_full_unstemmed | Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy |
| title_short | Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy |
| title_sort | identification and optimization of peptide inhibitors to block vista psgl 1 interaction for cancer immunotherapy |
| topic | Immune checkpoint VISTA PSGL-1 Phage displayed bio-panning Peptide Cancer immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523002940 |
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