Anti-CD47 antibodies: A potential new cancer immunotherapy

Objective: Immune checkpoint inhibitors, particularly anti-programmed cell death protein 1 (PDCD1/PD-1), anti-CD274 molecule (CD274/PD-L1), or anti-cytotoxic T-lymphocyte-associated protein 4 inhibitors, have shown notable anticancer efficacy in 10%–40% of cancer patients and >10 different cancer types. However, they have also reached an impasse. Therefore, targeting tumor-associated myeloid immune cells has become another viable approach. The CD47 molecule (CD47) is a “do not eat me” signal to phagocytes widely expressed in various tumor cells as a potential immune surveillance evasion mechanism. CD47 receptor signal-regulating protein alpha (SIRPα) is expressed in myeloid immune cells and inhibiting the CD47-SIRPα signaling pathway leads to tumor cell phagocytosis. Data Sources: We organized and presented the preclinical research of anti-CD47 in the past 40 years, and we also reviewed the results of anti-CD47-based clinical trials from 2018 to 2022. Study Selection: All studies we cited focus on using anti-CD47 blocking agents for targeting CD47/SIRPα. Results: In preclinical studies, anti-CD47 showed effectiveness in inducing macrophage phagocytosis of both solid tumors and blood cancers. However, clinically, anti-CD47 can only produce effective therapeutic effects when combined with other drugs, especially in treating blood cancers. Anti-CD47 may depend on directly regulating macrophage phagocytosis, tumor antigen capture by dendritic cells, and open adaptive immunity through cross-priming. Conclusion: Ongoing studies are investigating anti-CD47 in combination with chemotherapy, radiotherapy, targeted therapy, and immunomodulatory agents. Their results are eagerly awaited and will help clinical practice.