CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy

• DOI: 10.1136/jitc-2020-000905
• Publication Date: 2020-10-05T21:28:43Z
• Authors: 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
• Keywords: CD47; Cancer Immunotherapy

Background Immunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate cells, macrophages play roles in maintaining homeostasis, preventing pathogen invasion, resisting and promoting adaptive response. CD47 is found to be overexpressed on act as don’t eat me’ signal, which contributes evasion. Macrophages mediated phagocytosis blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved induce effective antitumor Methods A novel peptide pep-20, specifically targeting blocking interaction, identified high-throughput phage display library bio-panning. The capability enhance the macrophage-mediated activities effects pep-20 were investigated. mechanism T-cell response explored by ex vivo analysis confirmed macrophage depleting strategy. structure-activity relationship D-amino acid substitution also studied. proteolysis resistant derivate pep-20-D12 combined with irradiation (IR) Results Pep-20 showed enhancement both solid hematologic vitro, inhibited growth immune-competent tumor-bearing mice. Furthermore, promoted mobilize minimal toxicity. systemic administration robust synergistic efficacy combination IR. Conclusion In summary, these results demonstrated peptides, its derivate, could serve promising candidates promote macrophages-mediated cancer immunotherapy.