CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy
Background Immunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting a...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2020-10-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e000905.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850196913750540288 |
|---|---|
| author | Hongfei Wang Yixuan Sun Xiuman Zhou Chunxia Chen Ling Jiao Wanqiong Li Shanshan Gou Yanying Li Jiangfeng Du Guanyu Chen Wenjie Zhai Yahong Wu Yuanming Qi Yanfeng Gao |
| author_facet | Hongfei Wang Yixuan Sun Xiuman Zhou Chunxia Chen Ling Jiao Wanqiong Li Shanshan Gou Yanying Li Jiangfeng Du Guanyu Chen Wenjie Zhai Yahong Wu Yuanming Qi Yanfeng Gao |
| author_sort | Hongfei Wang |
| collection | DOAJ |
| description | Background Immunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting adaptive immune response. CD47 is found to be overexpressed on tumor cells and act as a don’t eat me’ signal, which contributes to immune evasion. Macrophages mediated phagocytosis via blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved to induce effective antitumor immune response.Methods A novel peptide pep-20, specifically targeting CD47 and blocking CD47/SIRPα interaction, was identified via high-throughput phage display library bio-panning. The capability to enhance the macrophage-mediated phagocytosis activities and antitumor effects of pep-20 were investigated. The mechanism of pep-20 to induce T-cell response was explored by ex vivo analysis and confirmed via macrophage depleting strategy. The structure-activity relationship and D-amino acid substitution of pep-20 were also studied. The antitumor effects and mechanism of a proteolysis resistant D-amino acid derivate pep-20-D12 combined with irradiation (IR) were also investigated.Results Pep-20 showed remarkable enhancement of macrophage-mediated phagocytosis to both solid and hematologic tumor cells in vitro, and inhibited tumor growth in immune-competent tumor-bearing mice. Furthermore, pep-20 promoted macrophages to mobilize the antitumor T-cell response with minimal toxicity. Furthermore, systemic administration of the derivate pep-20-D12 showed robust synergistic antitumor efficacy in combination with IR.Conclusion In summary, these results demonstrated that CD47/SIRPα blocking peptides, pep-20 and its derivate, could serve as promising candidates to promote macrophages-mediated phagocytosis and immune response in cancer immunotherapy. |
| format | Article |
| id | doaj-art-a73fbb488d6d4721a1bbd7f6e8073052 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a73fbb488d6d4721a1bbd7f6e80730522025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-000905CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapyHongfei Wang0Yixuan Sun1Xiuman Zhou2Chunxia Chen3Ling Jiao4Wanqiong Li5Shanshan Gou6Yanying Li7Jiangfeng Du8Guanyu Chen9Wenjie Zhai10Yahong Wu11Yuanming Qi12Yanfeng Gao131 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China1 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, China1 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China2 School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China1 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China1 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, ChinaSchool of Life Sciences, Zhengzhou University, Zhengzhou, China1 School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, ChinaBackground Immunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting adaptive immune response. CD47 is found to be overexpressed on tumor cells and act as a don’t eat me’ signal, which contributes to immune evasion. Macrophages mediated phagocytosis via blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved to induce effective antitumor immune response.Methods A novel peptide pep-20, specifically targeting CD47 and blocking CD47/SIRPα interaction, was identified via high-throughput phage display library bio-panning. The capability to enhance the macrophage-mediated phagocytosis activities and antitumor effects of pep-20 were investigated. The mechanism of pep-20 to induce T-cell response was explored by ex vivo analysis and confirmed via macrophage depleting strategy. The structure-activity relationship and D-amino acid substitution of pep-20 were also studied. The antitumor effects and mechanism of a proteolysis resistant D-amino acid derivate pep-20-D12 combined with irradiation (IR) were also investigated.Results Pep-20 showed remarkable enhancement of macrophage-mediated phagocytosis to both solid and hematologic tumor cells in vitro, and inhibited tumor growth in immune-competent tumor-bearing mice. Furthermore, pep-20 promoted macrophages to mobilize the antitumor T-cell response with minimal toxicity. Furthermore, systemic administration of the derivate pep-20-D12 showed robust synergistic antitumor efficacy in combination with IR.Conclusion In summary, these results demonstrated that CD47/SIRPα blocking peptides, pep-20 and its derivate, could serve as promising candidates to promote macrophages-mediated phagocytosis and immune response in cancer immunotherapy.https://jitc.bmj.com/content/8/2/e000905.full |
| spellingShingle | Hongfei Wang Yixuan Sun Xiuman Zhou Chunxia Chen Ling Jiao Wanqiong Li Shanshan Gou Yanying Li Jiangfeng Du Guanyu Chen Wenjie Zhai Yahong Wu Yuanming Qi Yanfeng Gao CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy Journal for ImmunoTherapy of Cancer |
| title | CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy |
| title_full | CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy |
| title_fullStr | CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy |
| title_full_unstemmed | CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy |
| title_short | CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy |
| title_sort | cd47 sirpα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy |
| url | https://jitc.bmj.com/content/8/2/e000905.full |
| work_keys_str_mv | AT hongfeiwang cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT yixuansun cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT xiumanzhou cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT chunxiachen cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT lingjiao cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT wanqiongli cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT shanshangou cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT yanyingli cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT jiangfengdu cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT guanyuchen cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT wenjiezhai cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT yahongwu cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT yuanmingqi cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy AT yanfenggao cd47sirpablockingpeptideidentificationandsynergisticeffectwithirradiationforcancerimmunotherapy |