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Published on: November 12, 2019
Potential New Cancer Immunotherapy: Anti-CD47-SIRPα Antibodies
Quansheng Lu1, Xi Chen1, Shan Wang2
1Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People's Republic of China.
Abstract:
CD47 belongs to immunoglobulin superfamily and is widely expressed on the surface of cell membrane, while another transmembrane protein SIRPα is restricted to the surface of macrophages, dendritic cells, and nerve cells. As a cell surface receptor and ligand, respectively, CD47 and SIRPα interact to regulate cell migration and phagocytic activity, and maintain immune homeostasis. In recent years, studies have found that immunoglobulin superfamily CD47 is overexpressed widely across tumor types, and CD47 plays an important role in suppressing phagocytes activity through binding to the transmembrane protein SIRPα in phagocytic cells. Therefore, targeting CD47 may be a novel strategy for cancer immunotherapy, and a variety of anti-CD47 antibodies have appeared, such as humanized 5F9 antibody, B6H12 antibody, ZF1 antibody, and so on. This review mainly describes the research history of CD47-SIRPα and focuses on macrophage-mediated CD47-SIRPα immunotherapy of tumors.
Insights
The CD47-SIRPα pathway suppresses immune responses. Targeting CD47 with antibodies offers a promising strategy for cancer immunotherapy by reactivating phagocytes to eliminate tumors.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- CD47, an immunoglobulin superfamily member, is broadly expressed on cell membranes.
- SIRPα is primarily found on immune cells like macrophages and dendritic cells.
- The CD47-SIRPα interaction regulates cell migration, phagocytosis, and immune homeostasis.
Purpose of the Study:
- To review the research history of the CD47-SIRPα interaction.
- To focus on macrophage-mediated immunotherapy targeting the CD47-SIRPα pathway in tumors.
Main Methods:
- Literature review of CD47-SIRPα interactions.
- Analysis of CD47 overexpression in various cancer types.
- Examination of anti-CD47 antibody-based immunotherapies.
Main Results:
- CD47 is overexpressed in numerous tumor types.
- CD47 binding to SIRPα inhibits phagocytosis by immune cells.
- Several anti-CD47 antibodies (e.g., 5F9, B6H12, ZF1) are under development.
Conclusions:
- Targeting CD47 represents a novel strategy for cancer immunotherapy.
- Re-engaging macrophages via CD47 blockade can promote tumor cell clearance.
- The CD47-SIRPα axis is a critical target for developing effective cancer treatments.
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