CD47/SIRPa Axis: "Don't Eat Me" Signal in Cancer Research

CD47 is a ubiquitously expressed "don't eat me" signal that protects cells from phagocytosis by macrophages. Tumor cells exploit this by overexpressing CD47 to evade innate immune surveillance. For an overview of all checkpoint targets, see our Immune Checkpoint Inhibitors guide.

Target Biology and Clinical Relevance

CD47 binds SIRPα (signal regulatory protein alpha) on macrophages, delivering an inhibitory signal that prevents phagocytic engulfment. Blocking the CD47-SIRPα interaction with anti-CD47 blocking antibodies or SIRPα-Fc decoy receptors enables macrophage-mediated tumor cell phagocytosis.

Unlike T cell checkpoints (PD-1, CTLA-4), the CD47-SIRPα axis operates through the innate immune system — specifically through tumor-associated macrophages within the tumor microenvironment. This makes it an attractive combination partner for adaptive checkpoint inhibitors (PD-1 + CD47 dual blockade). CD47 overexpression is particularly prominent in hematologic malignancies including AML, lymphoma, and MDS.

Research applications include: anti-CD47 blocking antibodies for phagocytosis assays, recombinant SIRPα ECD proteins for competitive binding and SPR/BLI kinetics, anti-CD47 flow cytometry antibodies for expression profiling, and research biosimilar anti-CD47 antibodies for preclinical efficacy studies and PK/ADA assays.

A key challenge in CD47 targeting is the "antigen sink" — CD47 is expressed on red blood cells and platelets, causing on-target/off-tumor toxicity (anemia, thrombocytopenia). Research into tumor-selective CD47 targeting strategies (bispecific antibodies, SIRPα-Fc) relies heavily on recombinant reagents.

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References

1. Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541-550. doi: 10.1038/s41591-018-0014-x

2. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264. doi: 10.1038/nrc3239

3. Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31-46. doi: 10.1158/2159-8290.CD-21-1059

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