Monocytes engineered with iSNAP inhibit human B‐lymphoma progression
Abstract Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47‐SIRPα recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10285 |
| _version_ | 1811251121584340992 |
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| author | Haohsiang Wu Siamak Amirfakhri Hsin‐Hung Lin Hannah Hollandsworth Filemoni Filemoni Yahan Liu Yiqian Wu Julie Y. S. Li Hongquan Xu Shu Chien Michael Bouvet Yingxiao Wang |
| author_facet | Haohsiang Wu Siamak Amirfakhri Hsin‐Hung Lin Hannah Hollandsworth Filemoni Filemoni Yahan Liu Yiqian Wu Julie Y. S. Li Hongquan Xu Shu Chien Michael Bouvet Yingxiao Wang |
| author_sort | Haohsiang Wu |
| collection | DOAJ |
| description | Abstract Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47‐SIRPα recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has been well‐known as the “Don't eat me” signal. By using an approach of integrated sensing and activating proteins (iSNAPs), we have rewired the CD47‐SIRPα axis to create iSNAP‐M which activates pathways in engineered human monocytes (iSNAP‐MC). The mRNA expression levels of the monocyte/macrophage markers CD11b, CD14, and CD31 are upregulated in iSNAP‐monocytes (iSNAP‐MC). With PMA induction, the iSNAP‐MC‐derived macrophages (iSNAP‐MΦ) showed upregelation in CD86 and CD80, but not CD206. TNFα expression and secretion were also increased in iSNAP‐MΦ. Furthermore, the injection of iSNAP‐MC into mice bearing human B‐lymphoma tumors led to the suppression of tumor progression. Therefore, the engineered monocytes, via blockage of coinhibitory immune signals by rewiring CD47‐SIRPα axis, can be applied to suppress target tumors for cancer immunotherapy. |
| first_indexed | 2024-04-12T16:14:58Z |
| format | Article |
| id | doaj.art-cb1aef40ea5346f489a4132f5d122cc7 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-04-12T16:14:58Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-cb1aef40ea5346f489a4132f5d122cc72022-12-22T03:25:46ZengWileyBioengineering & Translational Medicine2380-67612022-05-0172n/an/a10.1002/btm2.10285Monocytes engineered with iSNAP inhibit human B‐lymphoma progressionHaohsiang Wu0Siamak Amirfakhri1Hsin‐Hung Lin2Hannah Hollandsworth3Filemoni Filemoni4Yahan Liu5Yiqian Wu6Julie Y. S. Li7Hongquan Xu8Shu Chien9Michael Bouvet10Yingxiao Wang11Department of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USADepartment of Surgery, Moores Cancer Center University of California, San Diego San Diego California USADepartment of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USADepartment of Surgery, Moores Cancer Center University of California, San Diego San Diego California USADepartment of Surgery, Moores Cancer Center University of California, San Diego San Diego California USADepartment of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USADepartment of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USADepartment of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USADepartment of Statistics University of California Los Angeles California USADepartment of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USADepartment of Surgery, Moores Cancer Center University of California, San Diego San Diego California USADepartment of Bioengineering and Institute of Engineering in Medicine University of California San Diego San Diego California USAAbstract Monocytes are important regulators for the maintenance of homeostasis in innate and adaptive immune system and have been reported to play important role in cancer progression. CD47‐SIRPα recognition is a coinhibitory immune signal to inhibit phagocytosis in monocytes and macrophages and has been well‐known as the “Don't eat me” signal. By using an approach of integrated sensing and activating proteins (iSNAPs), we have rewired the CD47‐SIRPα axis to create iSNAP‐M which activates pathways in engineered human monocytes (iSNAP‐MC). The mRNA expression levels of the monocyte/macrophage markers CD11b, CD14, and CD31 are upregulated in iSNAP‐monocytes (iSNAP‐MC). With PMA induction, the iSNAP‐MC‐derived macrophages (iSNAP‐MΦ) showed upregelation in CD86 and CD80, but not CD206. TNFα expression and secretion were also increased in iSNAP‐MΦ. Furthermore, the injection of iSNAP‐MC into mice bearing human B‐lymphoma tumors led to the suppression of tumor progression. Therefore, the engineered monocytes, via blockage of coinhibitory immune signals by rewiring CD47‐SIRPα axis, can be applied to suppress target tumors for cancer immunotherapy.https://doi.org/10.1002/btm2.10285cancer immunotherapyCD47Don't eat me signalengineering monocytesmacrophage polarization |
| spellingShingle | Haohsiang Wu Siamak Amirfakhri Hsin‐Hung Lin Hannah Hollandsworth Filemoni Filemoni Yahan Liu Yiqian Wu Julie Y. S. Li Hongquan Xu Shu Chien Michael Bouvet Yingxiao Wang Monocytes engineered with iSNAP inhibit human B‐lymphoma progression Bioengineering & Translational Medicine cancer immunotherapy CD47 Don't eat me signal engineering monocytes macrophage polarization |
| title | Monocytes engineered with iSNAP inhibit human B‐lymphoma progression |
| title_full | Monocytes engineered with iSNAP inhibit human B‐lymphoma progression |
| title_fullStr | Monocytes engineered with iSNAP inhibit human B‐lymphoma progression |
| title_full_unstemmed | Monocytes engineered with iSNAP inhibit human B‐lymphoma progression |
| title_short | Monocytes engineered with iSNAP inhibit human B‐lymphoma progression |
| title_sort | monocytes engineered with isnap inhibit human b lymphoma progression |
| topic | cancer immunotherapy CD47 Don't eat me signal engineering monocytes macrophage polarization |
| url | https://doi.org/10.1002/btm2.10285 |
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