Seyed Mohammad Gheibi Hayat1, Vanessa Bianconi2, Matteo Pirro2, Mahmoud R Jaafari3,4, Mahdi Hatamipour3, Amirhossein Sahebkar5,6,7,8. 1. Student Research Committee, Department of Medical Biotechnology, Faculty Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy. 3. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir. 6. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir. 7. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. sahebkara@mums.ac.ir. 8. Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, P.O. Box: 91779-48564, Mashhad, Iran. sahebkara@mums.ac.ir.
Abstract
BACKGROUND: CD47 is a widely expressed cellular receptor well known for its immunoregulatory functions. By interacting with its ligands, including thrombospondin-1 (TSP-1), signal regulatory protein α (SIRPα), integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), it modulates cellular phagocytosis by macrophages, transmigration of neutrophils and activation of dendritic cells, T cells and B cells. Ample studies have shown that various types of cancer express high levels of CD47 to escape from the immune system. Based on this observation, CD47 is currently considered as a prominent target in cancer therapy. CONCLUSIONS: Here, we review the role of CD47 in the maintenance of immune system homeostasis. We also depict three emerging CD47-targeting strategies for cancer therapy, including the use of mimicry peptides, antibodies, and gene silencing strategies. Among these approaches, the most advanced one is the use of anti-CD47 antibodies, which enhances cancer cell phagocytosis via inhibition of the CD47-SIRPα axis. These antibodies can also achieve higher anti-cancer efficacies when combined with chemotherapy and immunotherapy and hold promise for improving the survival of patients with cancer.
BACKGROUND:CD47 is a widely expressed cellular receptor well known for its immunoregulatory functions. By interacting with its ligands, including thrombospondin-1 (TSP-1), signal regulatory protein α (SIRPα), integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), it modulates cellular phagocytosis by macrophages, transmigration of neutrophils and activation of dendritic cells, T cells and B cells. Ample studies have shown that various types of cancer express high levels of CD47 to escape from the immune system. Based on this observation, CD47 is currently considered as a prominent target in cancer therapy. CONCLUSIONS: Here, we review the role of CD47 in the maintenance of immune system homeostasis. We also depict three emerging CD47-targeting strategies for cancer therapy, including the use of mimicry peptides, antibodies, and gene silencing strategies. Among these approaches, the most advanced one is the use of anti-CD47 antibodies, which enhances cancer cell phagocytosis via inhibition of the CD47-SIRPα axis. These antibodies can also achieve higher anti-cancer efficacies when combined with chemotherapy and immunotherapy and hold promise for improving the survival of patients with cancer.
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