A second-generation M1-polarized CAR macrophage with antitumor efficacy
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc..
Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Nature immunology - 25(2024), 1 vom: 01. Jan., Seite 102-116 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lei, Anhua [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 04.01.2024 Date Revised 01.03.2024 published: Print-Electronic ErratumIn: Nat Immunol. 2023 Dec 18;:. - PMID 38110523 Citation Status MEDLINE |
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| doi: |
10.1038/s41590-023-01687-8 |
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| funding: |
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NLM365036064 |
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| 520 | |a Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages | ||
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| 700 | 1 | |a Yu, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Hengxing |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Xizhong |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Tianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hailing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Mengmeng |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xudong |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Siyu |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Dixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shaolong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuge |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Wanrun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Wenhong |e verfasserin |4 aut | |
| 700 | 1 | |a Church, George |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Francis Ka-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Zhihua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
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