CD47

Overview

CD47 is a cell surface transmembrane protein that is expressed at low levels by nearly all cells of the human body and plays a key role in the immune system recognition of "self" and macrophage phagocytic activity. Some cancer cells, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and multiple myeloma (MM), overexpress CD47 as a means of escaping phagocytosis. 1-3


  • Macrophages are part of the innate immune system, and they represent the first line of defense and respond quickly to threats such as tissue damage or infection.1
  • Similar to T cells, macrophages express a checkpoint receptor called signal regulatory protein α (SIRPα, also known as CD172a), which recognizes the surface receptor CD47 as a ligand on target cells.1
  • The interaction between SIRPα and CD47 initiates a signaling cascade that results in the inhibition of macrophage phagocytic activity, hence referred as the "Don't Eat Me" signal.1
  • Of note, red blood cells (RBCs) begin to express phagocytic signals as they age, therefore, blocking of their "Don't Eat Me" signal via a CD47 antibody may leads to undesired RBC degradation and toxicity.3,4

IMPLICATIONS IN CANCER

CD47 has been shown to commonly overexpressed on cancer cells, including hematologic malignancies and numerous solid cancers. 1-3

  • Cancer cells exploit the CD47-SIRPα pathway by overexpressing CD47 and sending a strong, anti-phagocytic "Don't Eat Me" signal to the immune system. 2
  • Inhibition of CD47-SIRPα binding through CD47 blockade can neutralize the "Don't Eat Me" signal and expose a cancer cell's "Eat Me signal".2

Oncogenic Expression

Substantial CD47 expression was detected in a variety of solid cancer types1-5including:

  • AML/MDS

    • Primary AML patient samples displayed increased expression of CD47 on the cell surface compared to normal cell counterparts.2
    • CD47 was highly expressed in ~25% of primary AML samples with low-moderate expression in the remainder.5
  • MM

    • CD47 expression was found to be profoundly higher in myeloma cells compared to other populations in patient peripheral blood mononuclear cells (PBMCs).1
  1. Sun J, et al. "Targeting CD47 as a Novel Immunotherapy for Multiple Myeloma". Cancers (Basel). 2020 Feb; 12(2): 305.
  2. Chao MP, et al. "Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies". Front Oncol. 2020 Jan 22;9:1380.
  3. Zhang W, et al. "Advances in Anti-Tumor Treatments Targeting the CD47/SIRPα Axis". Front Immunol. 2020 Jan 28;11:18.
  4. Berlin J, et al. "A first-in-human study of lemzoparlimab, a differentiated anti-CD47 antibody, in subjects with relapsed/refractory malignancy: initial monotherapy results". Society for Immunotherapy of Cancer (SITC) 2020 Annual Meeting. Abstract 385.
  5. Galli S et al. "CD47 protein expression in acute myeloid leukemia: A tissue microarray-based analysis". Leuk Res. 2015 Jul;39(7):749-56.

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