Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies

Evangelia Bolli; Maximilian  Scherger; Sana Arnouk; Ana Rita Pombo Antunes; David Straßburger; Moritz Urschbach; Judith  Stickdorn; Karen De Vlaminck; Kiavash Movahedi; Hans Joachim  Räder; Sophie Hernot; Pol  Besenius; Jo Van Ginderachter; Lutz Nuhn

doi:10.1002/advs.202004574

Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies

Evangelia Bolli, Maximilian Scherger, Sana Arnouk, Ana Rita Pombo Antunes, David Straßburger, Moritz Urschbach, Judith Stickdorn, Karen De Vlaminck, Kiavash Movahedi, Hans Joachim Räder, Sophie Hernot, Pol Besenius, Jo Van Ginderachter, Lutz Nuhn

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23 Citations (Scopus)

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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.

Original language	English
Article number	2004574
Number of pages	12
Journal	Advanced Science
Volume	8
Issue number	10
DOIs	https://doi.org/10.1002/advs.202004574
Publication status	Published - 19 May 2021

Bibliographical note

Funding Information:
E.B., M.S., and S.M.A. contributed equally to this work. All authors gratefully acknowledge support by the DFG Emmy Noether program and the SFB1066. Moreover, they are grateful to the support by the FWO Flanders and Kom op tegen Kanker as well as the Fonds der Chemischen Industrie for support by their Liebig program.

Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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10.1002/advs.202004574Licence: CC BY

66893901Final published version, 4.91 MBLicence: CC BY

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1 Finished
2 Active

SRP50: SRP-Onderzoekszwaartepunt: Exploiting Peptides: Protein Binders, Modulators and Inhibitors for Imaging and Therapy [Exploit-PeptIT]
Ballet, S., Caveliers, V., Hernot, S., Versées, W., Vinken, M., Muyldermans, S., Devoogdt, N., Bridoux, J. & Martin, C.
1/03/19 → 29/02/24
Project: Fundamental
IOF3005: IOF GEAR: NLITE
Lahoutte, T., Kuijk, M., Hernot, S. & Ingelberts, H.
21/12/18 → 20/12/23
Project: Applied
SRP47: Strategic Research Programme: Molecular Imaging and targeting of macrophages in Inflammation (ITARMI)
Lahoutte, T., Van Ginderachter, J. & Devoogdt, N.
1/11/17 → 31/10/22
Project: Fundamental

Cite this

Bolli, E., Scherger, M., Arnouk, S., Pombo Antunes, A. R., Straßburger, D., Urschbach, M., Stickdorn, J., De Vlaminck, K., Movahedi, K., Räder, H. J., Hernot, S., Besenius, P., Van Ginderachter, J., & Nuhn, L. (2021). Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies. Advanced Science, 8(10), [2004574]. https://doi.org/10.1002/advs.202004574

Bolli, Evangelia ; Scherger, Maximilian ; Arnouk, Sana ; Pombo Antunes, Ana Rita ; Straßburger, David ; Urschbach, Moritz ; Stickdorn, Judith ; De Vlaminck, Karen ; Movahedi, Kiavash ; Räder, Hans Joachim ; Hernot, Sophie ; Besenius, Pol ; Van Ginderachter, Jo ; Nuhn, Lutz. / Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies. In: Advanced Science. 2021 ; Vol. 8, No. 10.

@article{b7c16f1d331e4c609a465c451871e1b9,

title = "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 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.",

author = "Evangelia Bolli and Maximilian Scherger and Sana Arnouk and {Pombo Antunes}, {Ana Rita} and David Stra{\ss}burger and Moritz Urschbach and Judith Stickdorn and {De Vlaminck}, Karen and Kiavash Movahedi and R{\"a}der, {Hans Joachim} and Sophie Hernot and Pol Besenius and {Van Ginderachter}, Jo and Lutz Nuhn",

note = "Funding Information: E.B., M.S., and S.M.A. contributed equally to this work. All authors gratefully acknowledge support by the DFG Emmy Noether program and the SFB1066. Moreover, they are grateful to the support by the FWO Flanders and Kom op tegen Kanker as well as the Fonds der Chemischen Industrie for support by their Liebig program. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

day = "19",

doi = "10.1002/advs.202004574",

language = "English",

volume = "8",

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Bolli, E, Scherger, M, Arnouk, S , Pombo Antunes, AR, Straßburger, D, Urschbach, M, Stickdorn, J, De Vlaminck, K , Movahedi, K, Räder, HJ, Hernot, S, Besenius, P, Van Ginderachter, J & Nuhn, L 2021, 'Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies', Advanced Science, vol. 8, no. 10, 2004574. https://doi.org/10.1002/advs.202004574

Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies. / Bolli, Evangelia; Scherger, Maximilian ; Arnouk, Sana ; Pombo Antunes, Ana Rita; Straßburger, David; Urschbach, Moritz; Stickdorn, Judith ; De Vlaminck, Karen ; Movahedi, Kiavash; Räder, Hans Joachim ; Hernot, Sophie; Besenius, Pol; Van Ginderachter, Jo; Nuhn, Lutz.

In: Advanced Science, Vol. 8, No. 10, 2004574, 19.05.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies

AU - Bolli, Evangelia

AU - Scherger, Maximilian

AU - Arnouk, Sana

AU - Pombo Antunes, Ana Rita

AU - Straßburger, David

AU - Urschbach, Moritz

AU - Stickdorn, Judith

AU - De Vlaminck, Karen

AU - Movahedi, Kiavash

AU - Räder, Hans Joachim

AU - Hernot, Sophie

AU - Besenius, Pol

AU - Van Ginderachter, Jo

AU - Nuhn, Lutz

N1 - Funding Information: E.B., M.S., and S.M.A. contributed equally to this work. All authors gratefully acknowledge support by the DFG Emmy Noether program and the SFB1066. Moreover, they are grateful to the support by the FWO Flanders and Kom op tegen Kanker as well as the Fonds der Chemischen Industrie for support by their Liebig program. Publisher Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/19

Y1 - 2021/5/19

N2 - 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.

AB - 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.

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U2 - 10.1002/advs.202004574

DO - 10.1002/advs.202004574

M3 - Article

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SN - 2198-3844

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Targeted Repolarization of Tumor-Associated Macrophages via Imidazoquinoline-Linked Nanobodies

Abstract

Bibliographical note

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Projects

SRP50: SRP-Onderzoekszwaartepunt: Exploiting Peptides: Protein Binders, Modulators and Inhibitors for Imaging and Therapy [Exploit-PeptIT]

IOF3005: IOF GEAR: NLITE

SRP47: Strategic Research Programme: Molecular Imaging and targeting of macrophages in Inflammation (ITARMI)

Cite this