Blockade of CD47 or SIRPα: a new cancer immunotherapy

ABSTRACT

The CD47-Signal regulatory protein α (SIRPα) singling axis acts as a crucial regulator that limits the phagocytic activity of professional phagocytes such as macrophages. Recent studies have demonstrated that the interaction between CD47 on tumor cells and SIRPα on macrophages is implicated in the ability of tumors to evade immunosurveillance. Targeting the CD47-SIRPα interaction is therefore considered to be a promising approach for cancer therapy. Herein, we review some of studies displaying the potential clinical application of antibodies and other modalities that target the CD47-SIRPα interaction. Current limitations of the CD47-SIRPα-targeted immunotherapeutic approaches are also discussed as well as other avenues for future study to improve the current strategies in targeting the CD47-SIRPα signaling axis for cancer immunotherapy.

KEYWORDS:

• Cancer
• CD47
• immunotherapy
• macrophage
• phagocytosis
• SIRPα

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is employed by a company has interests in anti-SIRPα antibody R&D.

Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by Grants-in-Aid for Scientific Research (A) (grant number 18H04032 to T.M.) and (C) (grant number 19K07385 to Y.M.) from the Japan Society for the Promotion of Science and the Project for Cancer Research and Therapeutic Evolution (P-CREATE) from the Japan Agency for Medical Research and Development (AMED) (to T.M.).