An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma
Abstract The cytokine interleukin (IL)‐11 has been shown to play a role in promoting fibrosis and cancer, including lung adenocarcinoma, garnering interest as an attractive target for therapeutic intervention. We used combinatorial methods to engineer an IL‐11 variant that binds with higher affinity...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-11-01
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| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10573 |
| _version_ | 1827708704803258368 |
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| author | Brianna J. McIntosh Griffin G. Hartmann Sean A. Yamada‐Hunter Phillip Liu Camille F. Williams Julien Sage Jennifer R. Cochran |
| author_facet | Brianna J. McIntosh Griffin G. Hartmann Sean A. Yamada‐Hunter Phillip Liu Camille F. Williams Julien Sage Jennifer R. Cochran |
| author_sort | Brianna J. McIntosh |
| collection | DOAJ |
| description | Abstract The cytokine interleukin (IL)‐11 has been shown to play a role in promoting fibrosis and cancer, including lung adenocarcinoma, garnering interest as an attractive target for therapeutic intervention. We used combinatorial methods to engineer an IL‐11 variant that binds with higher affinity to the IL‐11 receptor and stimulates enhanced receptor‐mediated cell signaling. Introduction of two additional point mutations ablates IL‐11 ligand/receptor association with the gp130 coreceptor signaling complex, resulting in a high‐affinity receptor antagonist. Unlike wild‐type IL‐11, this engineered variant potently blocks IL‐11‐mediated cell signaling and slows tumor growth in a mouse model of lung cancer. Our approach highlights a strategy where native ligands can be engineered and exploited to create potent receptor antagonists. |
| first_indexed | 2024-03-10T17:09:24Z |
| format | Article |
| id | doaj.art-e074518fcf654bf4858ad1a87a84c9f0 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-10T17:09:24Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-e074518fcf654bf4858ad1a87a84c9f02023-11-20T10:44:12ZengWileyBioengineering & Translational Medicine2380-67612023-11-0186n/an/a10.1002/btm2.10573An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinomaBrianna J. McIntosh0Griffin G. Hartmann1Sean A. Yamada‐Hunter2Phillip Liu3Camille F. Williams4Julien Sage5Jennifer R. Cochran6Cancer Biology Program Stanford University Stanford California USACancer Biology Program Stanford University Stanford California USACenter for Cancer Cell Therapy, Stanford Cancer Institute Stanford University School of Medicine Stanford California USABiophysics Program Stanford University Stanford California USADepartment of Chemistry Stanford University Stanford California USADepartment of Pediatrics Stanford University Stanford California USACancer Biology Program Stanford University Stanford California USAAbstract The cytokine interleukin (IL)‐11 has been shown to play a role in promoting fibrosis and cancer, including lung adenocarcinoma, garnering interest as an attractive target for therapeutic intervention. We used combinatorial methods to engineer an IL‐11 variant that binds with higher affinity to the IL‐11 receptor and stimulates enhanced receptor‐mediated cell signaling. Introduction of two additional point mutations ablates IL‐11 ligand/receptor association with the gp130 coreceptor signaling complex, resulting in a high‐affinity receptor antagonist. Unlike wild‐type IL‐11, this engineered variant potently blocks IL‐11‐mediated cell signaling and slows tumor growth in a mouse model of lung cancer. Our approach highlights a strategy where native ligands can be engineered and exploited to create potent receptor antagonists.https://doi.org/10.1002/btm2.10573cancer progressioncytokinesIL‐11ligand/receptor interactionprotein engineering |
| spellingShingle | Brianna J. McIntosh Griffin G. Hartmann Sean A. Yamada‐Hunter Phillip Liu Camille F. Williams Julien Sage Jennifer R. Cochran An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma Bioengineering & Translational Medicine cancer progression cytokines IL‐11 ligand/receptor interaction protein engineering |
| title | An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma |
| title_full | An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma |
| title_fullStr | An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma |
| title_full_unstemmed | An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma |
| title_short | An engineered interleukin‐11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma |
| title_sort | engineered interleukin 11 decoy cytokine inhibits receptor signaling and proliferation in lung adenocarcinoma |
| topic | cancer progression cytokines IL‐11 ligand/receptor interaction protein engineering |
| url | https://doi.org/10.1002/btm2.10573 |
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