T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles

Verena Turco, Kira Pfleiderer, Jessica Hunger, Natalie K. Horvat, Kianush Karimian-Jazi, Katharina Schregel, Manuel Fischer, Gianluca Brugnara, Kristine Jähne, Volker Sturm, Yannik Streibel, Duy Nguyen, Sandro Altamura, Dennis A. Agardy, Shreya S. Soni, Abdulrahman Alsasa, Theresa Bunse, Matthias Schlesner, Martina U. Muckenthaler, Ralph Weissleder, Wolfgang Wick, Sabine Heiland, Philipp Vollmuth, Martin Bendszus, Christopher B. Rodell, Michael O. Breckwoldt () and Michael Platten ()
Additional contact information
Verena Turco: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Kira Pfleiderer: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Jessica Hunger: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Natalie K. Horvat: Heidelberg University
Kianush Karimian-Jazi: University Hospital Heidelberg
Katharina Schregel: University Hospital Heidelberg
Manuel Fischer: University Hospital Heidelberg
Gianluca Brugnara: University Hospital Heidelberg
Kristine Jähne: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Volker Sturm: University Hospital Heidelberg
Yannik Streibel: University Hospital Heidelberg
Duy Nguyen: DKFZ
Sandro Altamura: University Hospital
Dennis A. Agardy: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Shreya S. Soni: Drexel University
Abdulrahman Alsasa: Drexel University
Theresa Bunse: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Matthias Schlesner: DKFZ
Martina U. Muckenthaler: University Hospital
Ralph Weissleder: Massachusetts General Hospital
Wolfgang Wick: DKTK within DKFZ
Sabine Heiland: University Hospital Heidelberg
Philipp Vollmuth: University Hospital Heidelberg
Martin Bendszus: University Hospital Heidelberg
Christopher B. Rodell: Drexel University
Michael O. Breckwoldt: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
Michael Platten: German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically “cold” tumor with sparse infiltration by adaptive immune cells. Immunosuppressive tumor-associated myeloid cells are drivers of tumor progression. Therefore, targeting and reprogramming intratumoral myeloid cells is an appealing therapeutic strategy. Here, we investigate a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating the Toll-like receptor 7 and 8 (TLR7/8) agonist R848 (CDNP-R848) to reprogram myeloid cells in the glioma microenvironment. We show that intravenous monotherapy with CDNP-R848 induces regression of established syngeneic experimental glioma, resulting in increased survival rates compared with unloaded CDNP controls. Mechanistically, CDNP-R848 treatment reshapes the immunosuppressive tumor microenvironment and orchestrates tumor clearing by pro-inflammatory tumor-associated myeloid cells, independently of T cells and NK cells. Using serial magnetic resonance imaging, we identify a radiomic signature in response to CDNP-R848 treatment and ultrasmall superparamagnetic iron oxide (USPIO) imaging reveals that immunosuppressive macrophage recruitment is reduced by CDNP-R848. In conclusion, CDNP-R848 induces tumor regression in experimental glioma by targeting blood-borne macrophages without requiring adaptive immunity.

Date: 2023
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Citations: View citations in EconPapers (2)

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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36321-6

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DOI: 10.1038/s41467-023-36321-6

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