Chimeric antigen receptors that trigger phagocytosis

Morrissey, M. A., Williamson, A. P., Steinbach, A. M., Roberts, E. W. , Kern, N., Headley, M. B. and Vale, R. D. (2018) Chimeric antigen receptors that trigger phagocytosis. eLife, 7, e36688. (doi: 10.7554/eLife.36688.001) (PMID:29862966) (PMCID:PMC6008046)

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%.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Roberts, Dr Ed

Creator Roles

Roberts, E.: Conceptualization, Resources, Formal analysis, Investigation, Methodology, Writing – review and editing

• Authors: Morrissey, M. A., Williamson, A. P., Steinbach, A. M., Roberts, E. W., Kern, N., Headley, M. B., and Vale, R. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: eLife
• Publisher: eLife Sciences Publications
• ISSN: 2050-084X
• ISSN (Online): 2050-084X
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in eLife 7:e36688
• Publisher Policy: Reproduced under a Creative Commons License