Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies
Abstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonis...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202004574 |
| _version_ | 1818915141187534848 |
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| author | Evangelia Bolli Maximilian Scherger Sana M. Arnouk Ana Rita Pombo Antunes David Straßburger Moritz Urschbach Judith Stickdorn Karen De Vlaminck Kiavash Movahedi Hans Joachim Räder Sophie Hernot Pol Besenius Jo A. Van Ginderachter Lutz Nuhn |
| author_facet | Evangelia Bolli Maximilian Scherger Sana M. Arnouk Ana Rita Pombo Antunes David Straßburger Moritz Urschbach Judith Stickdorn Karen De Vlaminck Kiavash Movahedi Hans Joachim Räder Sophie Hernot Pol Besenius Jo A. Van Ginderachter Lutz Nuhn |
| author_sort | Evangelia Bolli |
| collection | DOAJ |
| description | Abstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonist imidazoquinoline IMDQ is site‐specifically and quantitatively coupled to single chain antibody fragments, so‐called nanobodies, targeting the macrophage mannose receptor (MMR) on TAMs. Intravenous injection of these conjugates result in a tumor‐ and cell‐specific delivery of IMDQ into MMRhigh TAMs, causing a significant decline in tumor growth. This is accompanied by a repolarization of TAMs towards a pro‐inflammatory phenotype and an increase in anti‐tumor T cell responses. Therefore, the therapeutic benefit of such nanobody‐drug conjugates may pave the road towards effective macrophage re‐educating cancer immunotherapies. |
| first_indexed | 2024-12-19T23:57:33Z |
| format | Article |
| id | doaj.art-cac8fa4c5d6f47508fc134a4bcd703ea |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-19T23:57:33Z |
| publishDate | 2021-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-cac8fa4c5d6f47508fc134a4bcd703ea2022-12-21T20:00:58ZengWileyAdvanced Science2198-38442021-05-01810n/an/a10.1002/advs.202004574Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked NanobodiesEvangelia Bolli0Maximilian Scherger1Sana M. Arnouk2Ana Rita Pombo Antunes3David Straßburger4Moritz Urschbach5Judith Stickdorn6Karen De Vlaminck7Kiavash Movahedi8Hans Joachim Räder9Sophie Hernot10Pol Besenius11Jo A. Van Ginderachter12Lutz Nuhn13Lab of Cellular and Molecular Immunology Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 BelgiumMax Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 GermanyLab of Cellular and Molecular Immunology Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 BelgiumLab of Cellular and Molecular Immunology Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 BelgiumDepartment of Chemistry Johannes Gutenberg‐University Mainz Duesbergweg 10‐14 Mainz 55128 GermanyDepartment of Chemistry Johannes Gutenberg‐University Mainz Duesbergweg 10‐14 Mainz 55128 GermanyMax Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 GermanyLab of Cellular and Molecular Immunology Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 BelgiumLab of Cellular and Molecular Immunology Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 BelgiumMax Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 GermanyLaboratory of In Vivo Cellular and Molecular Imaging Vrije Universiteit Brussel Laarbeeklaan 103 Brussels 1090 BelgiumDepartment of Chemistry Johannes Gutenberg‐University Mainz Duesbergweg 10‐14 Mainz 55128 GermanyLab of Cellular and Molecular Immunology Vrije Universiteit Brussel Pleinlaan 2 Brussels 1050 BelgiumMax Planck Institute for Polymer Research Ackermannweg 10 Mainz 55128 GermanyAbstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonist imidazoquinoline IMDQ is site‐specifically and quantitatively coupled to single chain antibody fragments, so‐called nanobodies, targeting the macrophage mannose receptor (MMR) on TAMs. Intravenous injection of these conjugates result in a tumor‐ and cell‐specific delivery of IMDQ into MMRhigh TAMs, causing a significant decline in tumor growth. This is accompanied by a repolarization of TAMs towards a pro‐inflammatory phenotype and an increase in anti‐tumor T cell responses. Therefore, the therapeutic benefit of such nanobody‐drug conjugates may pave the road towards effective macrophage re‐educating cancer immunotherapies.https://doi.org/10.1002/advs.202004574cancer immunotherapydrug deliveryM2 macrophagesnanobodiesrepolarizationTLR 7/8 agonist |
| spellingShingle | Evangelia Bolli Maximilian Scherger Sana M. Arnouk Ana Rita Pombo Antunes David Straßburger Moritz Urschbach Judith Stickdorn Karen De Vlaminck Kiavash Movahedi Hans Joachim Räder Sophie Hernot Pol Besenius Jo A. Van Ginderachter Lutz Nuhn Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies Advanced Science cancer immunotherapy drug delivery M2 macrophages nanobodies repolarization TLR 7/8 agonist |
| title | Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies |
| title_full | Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies |
| title_fullStr | Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies |
| title_full_unstemmed | Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies |
| title_short | Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies |
| title_sort | targeted repolarization of tumor associated macrophages via imidazoquinoline linked nanobodies |
| topic | cancer immunotherapy drug delivery M2 macrophages nanobodies repolarization TLR 7/8 agonist |
| url | https://doi.org/10.1002/advs.202004574 |
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