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Chimeric antigen receptors that trigger phagocytosis. | LitMetric

Chimeric antigen receptors that trigger phagocytosis.

Elife

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.

Published: June 2018

AI Article Synopsis

Article Abstract

Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T cells to kill cancer. The success of CAR-T cell therapies highlights the promise of programmed immunity and suggests that applying CAR strategies to other immune cell lineages may be beneficial. Here, we engineered a family of Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that direct macrophages to engulf specific targets, including cancer cells. CAR-Ps consist of an extracellular antibody fragment, which can be modified to direct CAR-P activity towards specific antigens. By screening a panel of engulfment receptor intracellular domains, we found that the cytosolic domains from Megf10 and FcRɣ robustly triggered engulfment independently of their native extracellular domain. We show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole human cancer cells. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. Finally, we show that CAR-P expressing murine macrophages reduce cancer cell number in co-culture by over 40%.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008046PMC
http://dx.doi.org/10.7554/eLife.36688DOI Listing

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