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

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 immunotherapeu...

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Bibliographic Details
Main Authors: Weiskopf, Kipp, Ring, Aaron M, Schnorr, Peter J, Volkmer, Jens-Peter, Volkmer, Anne Kathrin, Weissman, Irving L, Garcia, K Christopher
Format: Online
Language:English
Published: Landes Bioscience 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850276/
Description
Summary: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.