Chimeric antigen receptors that trigger phagocytosis
- University of California, San Francisco, United States
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%.
Data availability
The replicates used to construct Figure 1d have been uploaded to Dryad (doi:10.5061/dryad.c57c1s0). Due to the large size of the datasets, the full set of raw images are available from the authors upon request.
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Replicates used to construct Figure 1D inAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
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Data from: Chimeric antigen receptors that trigger phagocytosisAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (F32GM120990)
- Meghan A Morrissey
Cancer Research Institute (Irvington Postdoctoral Fellowship)
- Adam P Williamson
Howard Hughes Medical Institute
- Ronald Vale
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice were maintained under specific pathogen-free conditions and treated in accordance with the regulatory standards of the NIH and American Association of Laboratory Animal Care standards, and are consistent with the UCSF Institution of Animal Care and Use Committee (IACUC approval: AN170208-01I).
Copyright
© 2018, Morrissey et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Chimeric antigen receptors that trigger phagocytosis
eLife 7:e36688.
https://doi.org/10.7554/eLife.36688
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