RNA with chemotherapeutic base analogues as a dual-functional anti-cancer drug.

Autor:	Jarzebska NT; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Science, University of Zürich, Zürich, Switzerland., Tusup M; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Medicine, University of Zürich, Zürich, Switzerland., Frei J; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Medicine, University of Zürich, Zürich, Switzerland., Weiss T; Department of Neurology and Clinical Neuroscience Center, University Hospital Zürich (USZ), University of Zürich (UZH), 8091, Zürich, Switzerland., Holzinger T; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Medicine, University of Zürich, Zürich, Switzerland., Mellett M; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Medicine, University of Zürich, Zürich, Switzerland., Diken M; BioNTech SE, Mainz, Germany., Bredl S; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich (USZ), University of Zürich (UZH), 8091, Zürich, Switzerland., Weller M; Department of Neurology and Clinical Neuroscience Center, University Hospital Zürich (USZ), University of Zürich (UZH), 8091, Zürich, Switzerland., Speck RF; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich (USZ), University of Zürich (UZH), 8091, Zürich, Switzerland., Kündig TM; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Medicine, University of Zürich, Zürich, Switzerland., Sahin U; BioNTech SE, Mainz, Germany., Pascolo S; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Raemistrasse 100, 8091, Zürich, Switzerland.; Faculty of Medicine, University of Zürich, Zürich, Switzerland.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2022 Nov 18; Vol. 11 (1), pp. 2147665. Date of Electronic Publication: 2022 Nov 18 (Print Publication: 2022).
DOI:	10.1080/2162402X.2022.2147665
Abstrakt:	Nanoparticles of different sizes formulated with unmodified RNA and Protamine differentially engage Toll-like Receptors (TLRs) and activate innate immune responses in vitro . Here, we report that similar differential immunostimulation that depends on the nanoparticle sizes is induced in vivo in wild type as well as in humanized mice. In addition, we found that the schedule of injections strongly affects the magnitude of the immune response. Immunostimulating 130 nm nanoparticles composed of RNA and Protamine can promote lung metastasis clearance but provides no control of subcutaneous tumors in a CT26 tumor model. We further enhanced the therapeutic capacity of Protamine-RNA nanoparticles by incorporating chemotherapeutic base analogues in the RNA; we coined these immunochemotherapeutic RNAs (icRNAs). Protamine-icRNA nanoparticles were successful at controlling established subcutaneous CT26 and B16 tumors as well as orthotopic glioblastoma. These data indicate that icRNAs are promising cancer therapies, which warrants their further validation for use in the clinic. Competing Interests: Steve Pascolo is the inventor on a patent “US10980875B2 Cytotoxic immunostimulating particles and uses thereof”. The other authors report there are no competing interests to declare. (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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