Novel fully human anti-CD47 antibodies stimulate phagocytosis and promote elimination of AML cells

J Cell Physiol. 2021 Jun;236(6):4470-4481. doi: 10.1002/jcp.30163. Epub 2020 Nov 18.

Abstract

Although most patients with acute myeloid leukemia (AML) enter remission after induction chemotherapy, the risk of relapse remains considerable. Therefore, some novel therapeutic strategies are still required. This study found that the overexpression of CD47 on AML cells was at least twofold more than that on normal bone marrow (NBM) cells in 81% (17/21) of the investigated patients; no patients had lower expression level of CD47 compared with healthy donors. The study also demonstrated that blocking the CD47/SIRPα (signal regulatory protein α) signal with the established novel fully human anti-CD47 monoclonal antibodies increased the phagocytosis of AML cells by macrophages in vitro. Furthermore, in vivo experiments showed that the novel fully human anti-CD47 monoclonal antibodies could significantly prolong the survival time of mice. Overall, the novel fully human anti-CD47 antibodies could block CD47/SIRPα interaction, increase macrophage-mediated phagocytosis, and enhance the elimination of AML cells.

Keywords: CD47; acute myeloid leukemia; immune checkpoint; macrophage; phagocytosis; therapeutic antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibody Specificity
  • Antigens, Differentiation / metabolism
  • Antineoplastic Agents, Immunological / pharmacology*
  • Binding Sites, Antibody
  • CD47 Antigen / antagonists & inhibitors*
  • CD47 Antigen / immunology
  • CD47 Antigen / metabolism
  • Case-Control Studies
  • Female
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Phagocytosis / drug effects*
  • Receptors, Immunologic / metabolism
  • THP-1 Cells
  • U937 Cells
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, Differentiation
  • Antineoplastic Agents, Immunological
  • CD47 Antigen
  • CD47 protein, human
  • Receptors, Immunologic
  • SIRPA protein, human