Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis

Mol Pharm. 2022 May 2;19(5):1273-1293. doi: 10.1021/acs.molpharmaceut.2c00073. Epub 2022 Apr 18.

Abstract

Cancer is still a major disease that is currently difficult for humans to overcome. When the expression of the cluster of differentiation 47 (CD47) is upregulated, tumor cells interact with the macrophage inhibitory receptor signal regulatory protein α (SIRPα) to transmit the "Don't eat me" signal, thereby avoiding phagocytosis by the macrophages. Therefore, when the CD47-SIRPα axis is inhibited, the macrophages' phagocytic function can be restored and can also exert antitumor effects. This Review mainly introduces recent advances in tumor therapy targeted on the CD47-SIRPα axis, including the antibody and fusion protein, small molecule, gene therapy, cell therapy, and drug delivery system, to inhibit the function of CD47 expressed on tumor cells and promote tumor phagocytosis by macrophages. In addition, this Review also summarizes the current approaches to avoid anemia, a common side effect of CD47-SIRPα inhibitions, and provides ideas for clinical transformation.

Keywords: CD47-SIRPα axis; anti-CD47 antibody; cell therapy; drug delivery system; liposome; nanoparticle.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / metabolism
  • Antigens, Differentiation / pharmacology
  • CD47 Antigen*
  • Humans
  • Immunotherapy
  • Neoplasms* / drug therapy
  • Phagocytosis
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism

Substances

  • Antigens, Differentiation
  • CD47 Antigen
  • CD47 protein, human
  • Receptors, Immunologic