Chimeric antigen receptors that trigger phagocytosis
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 o...
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2018-06-01
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doaj-b6c213511ca34e6e95a2eeaeb0ed02382021-05-05T15:54:21ZengeLife Sciences Publications LtdeLife2050-084X2018-06-01710.7554/eLife.36688Chimeric antigen receptors that trigger phagocytosisMeghan A Morrissey0https://orcid.org/0000-0002-0531-4864Adam P Williamson1https://orcid.org/0000-0001-8905-5646Adriana M Steinbach2Edward W Roberts3Nadja Kern4Mark B Headley5Ronald D Vale6https://orcid.org/0000-0003-3460-2758Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United StatesChimeric 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%.https://elifesciences.org/articles/36688Chimeric Antigen Receptorphagocytosismacrophagessignal transductionreceptorsFc Receptor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meghan A Morrissey Adam P Williamson Adriana M Steinbach Edward W Roberts Nadja Kern Mark B Headley Ronald D Vale |
spellingShingle |
Meghan A Morrissey Adam P Williamson Adriana M Steinbach Edward W Roberts Nadja Kern Mark B Headley Ronald D Vale Chimeric antigen receptors that trigger phagocytosis eLife Chimeric Antigen Receptor phagocytosis macrophages signal transduction receptors Fc Receptor |
author_facet |
Meghan A Morrissey Adam P Williamson Adriana M Steinbach Edward W Roberts Nadja Kern Mark B Headley Ronald D Vale |
author_sort |
Meghan A Morrissey |
title |
Chimeric antigen receptors that trigger phagocytosis |
title_short |
Chimeric antigen receptors that trigger phagocytosis |
title_full |
Chimeric antigen receptors that trigger phagocytosis |
title_fullStr |
Chimeric antigen receptors that trigger phagocytosis |
title_full_unstemmed |
Chimeric antigen receptors that trigger phagocytosis |
title_sort |
chimeric antigen receptors that trigger phagocytosis |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2018-06-01 |
description |
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%. |
topic |
Chimeric Antigen Receptor phagocytosis macrophages signal transduction receptors Fc Receptor |
url |
https://elifesciences.org/articles/36688 |
work_keys_str_mv |
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