Improving macrophage responses to therapeutic antibodies by molecular engineering of SIRPα variants

Oncoimmunology. 2013 Sep 1;2(9):e25773. doi: 10.4161/onci.25773. Epub 2013 Jul 29.


CD47 transduces inhibitory signals through signal-regulatory protein α (SIRPα), a plasma membrane receptor expressed by macrophages. Many cancers upregulate CD47 to evade immunosurveillance. We have recently engineered SIRPα variants that potently antagonize CD47 for use as anticancer immunotherapeutics. These high-affinity SIRPα variants synergize with antineoplastic antibodies by lowering the threshold for macrophage-mediated destruction of malignant cells.

Keywords: CD47; SIRPa; antibody; cancer; immune checkpoint; immunotherapy; macrophage; molecular engineering; phagocytosis.