CD47 is a novel potent immunotherapy target in human malignancies: current studies and future promises

Future Oncol. 2018 Sep;14(21):2179-2188. doi: 10.2217/fon-2018-0035. Epub 2018 Apr 18.

Abstract

Recently, many immunosuppressive checkpoints such as PD-L1, CTLA-4 and CD47, were identified in succession and serve as potential immunotherapy targets in human cancers. Among them, CD47, a 'marker-of-self' protein that is overexpressed broadly across tumor types, is emerging as a novel potent macrophage immune checkpoint for cancer immunotherapy. In this review, we highlight the prominent role of CD47 as a 'don't-eat-me' signal that inhibits macrophage phagocytosis for immune evasion of a tumor and presents the opportunities and challenges for CD47 inhibitors both as monotherapy and in combination treatments for hematological cancers and solid tumors; some of these agents are currently in clinical trials.

Keywords: CD47; CD47 blockade; SIRP; anti-CD47 monoclonal antibody; bispecific antibody; cancer; immune checkpoint inhibitor; immunotherapy; phagocytosis; tumor-associated macrophage.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • CD47 Antigen / antagonists & inhibitors
  • CD47 Antigen / chemistry
  • CD47 Antigen / genetics
  • CD47 Antigen / metabolism*
  • Combined Modality Therapy
  • Gene Expression
  • Humans
  • Immunotherapy*
  • Molecular Targeted Therapy
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • CD47 Antigen
  • CD47 protein, human