Immunotherapy of experimental melanoma with ICOS-Fc loaded in biocompatible and biodegradable nanoparticles.

Autor: Clemente N; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy., Boggio E; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy., Gigliotti LC; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy., Raineri D; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy; Center for Translational Research on Autoimmune and Allergic Disease-CAAD, Università del Piemonte Orientale, 28100 Novara, Italy., Ferrara B; Department of Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy., Miglio G; Department of Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy., Argenziano M; Department of Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy., Chiocchetti A; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy; Center for Translational Research on Autoimmune and Allergic Disease-CAAD, Università del Piemonte Orientale, 28100 Novara, Italy., Cappellano G; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy; Center for Translational Research on Autoimmune and Allergic Disease-CAAD, Università del Piemonte Orientale, 28100 Novara, Italy., Trotta F; Department of Chemistry, University of Torino, 10125 Torino, Italy., Caldera F; Department of Chemistry, University of Torino, 10125 Torino, Italy., Capucchio MT; Department of Veterinary Sciences, University of Torino, 10095 Grugliasco, TO, Italy., Yagi J; Department of Microbiology and Immunology, Tokyo Women's Medical University, Tokyo 108-8639, Japan., Rojo MJ; Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientıficas, 28040 Madrid, Spain., Renò F; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy., Cavalli R; Department of Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy. Electronic address: roberta.cavalli@unito.it., Dianzani C; Department of Scienza e Tecnologia del Farmaco, University of Torino, 10125 Torino, Italy., Dianzani U; Department of Health Sciences, Inter Interdisciplinary Research Center of Autoimmune Diseases, UPO, 28100 Novara, Italy; Center for Translational Research on Autoimmune and Allergic Disease-CAAD, Università del Piemonte Orientale, 28100 Novara, Italy.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2020 Apr 10; Vol. 320, pp. 112-124. Date of Electronic Publication: 2020 Jan 18.
DOI: 10.1016/j.jconrel.2020.01.030
Abstrakt: Inducible T-cell costimulator (ICOS) upon binding to its ligand (ICOSL) mediates adaptive immunity and antitumor response. Thus, antitumor therapies targeting the ICOS/ICOSL pathway hold great promise for cancer treatment. In this regard, ICOSL triggering by a soluble recombinant form of ICOS (ICOS-Fc) hampered adhesiveness and migration of dendritic, endothelial, and tumor cells in vitro. Furthermore, in vivo treatment with ICOS-Fc previously showed the capability to inhibit lung metastatization of ICOSL + B16-F10 melanoma cells when injected intravenously in mice, but it failed to block the growth of established subcutaneous B16-F10 murine tumors. Thus, we asked whether passive targeting of solid tumors with ICOS-Fc-loaded biocompatible and biodegradable nanoparticles (NPs) could instead prove effectiveness in reducing tumor growth. Here, ICOS-Fc was loaded in two types of polymer nanoparticles, i.e. cross-linked β-cyclodextrin nanosponges (CDNS) and poly(lactic-co-glycolic acid) (PLGA) NPs and in vitro characterized. In vivo experiments showed that treatment of C57BL6/J mice with ICOS-Fc loaded into the two nanoformulations inhibits the growth of established subcutaneous B16-F10 tumors. This anticancer activity appears to involve both anti-angiogenic and immunoregulatory effects, as shown by decreased tumor vascularization and downmodulation of IL-10 and Foxp3, two markers of regulatory T cells (Tregs). Overall, the substantial in vivo anticancer activity of ICOS-Fc-loaded CDNS and PLGA NPs against different components of the tumor microenvironment makes these nanoformulations attractive candidates for future combination cancer therapy.
Competing Interests: Declaration of Competing Interest A patent application has been submitted for use of ligands of ICOSL loaded in nanoparticles in tumors treatment.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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