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    Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors

    Autor: 
    Terán-Navarro, Hector
    ;
    Zeoli, Andrea
    ;
    Salines-Cuevas, David
    ;
    Marradi, Marco
    ;
    Montoya, Noemí
    ;
    Gonzalez-Lopez, Elena
    ;
    Ocejo-Vinyals, J. Gonzalo
    ;
    Dominguez-Esteban, Mario
    ;
    Gutierrez-Baños, Jose Luis
    ;
    Campos-Juanatey, Felix
    ;
    Yañez-Diaz, Sonsoles
    ;
    Garcia-Castaño, Almudena
    ;
    Rivera, Fernando
    ;
    Duran, Ignacio
    ;
    Álvarez-Domínguez, Carmen
    Fecha: 
    2022
    Palabra clave: 
    bladder cancer; immunotherapy; listeriolysin O; melanoma; nanoparticles; Scopus; JCR
    Tipo de Ítem: 
    Articulo Revista Indexada
    URI: 
    https://reunir.unir.net/handle/123456789/13978
    DOI: 
    https://doi.org/10.3390/cancers14102413
    Dirección web: 
    https://www.mdpi.com/2072-6694/14/10/2413
    Open Access
    Resumen:
    This study presents proof of concept assays to validate gold nanoparticles loaded with the bacterial peptide 91–99 of the listeriolysin O toxin (GNP-LLO91–99 nanovaccines) as immunotherapy for bladder tumors. GNP-LLO91–99 nanovaccines showed adjuvant abilities as they induce maturation and activation of monocyte-derived dendritic cells (MoDCs) to functional antigen-presenting cells in healthy donors and patients with melanoma or bladder cancer (BC), promoting a Th1 cytokine pattern. GNP-LLO91–99 nanovaccines were also efficient dendritic cell inducers of immunogenic tumor death using different bladder and melanoma tumor cell lines. The establishment of a pre-clinical mice model of subcutaneous BC confirmed that a single dose of GNP-LLO91–99 nanovaccines reduced tumor burden 4.7-fold and stimulated systemic Th1-type immune responses. Proof of concept assays validated GNP-LLO91–99 nanovaccines as immunotherapy by comparison to anti-CTLA-4 or anti-PD-1 antibodies. In fact, GNP-LLO91–99 nanovaccines increased percentages of CD4+ and CD8+ T cells, B cells, and functional antigen-presenting DCs in tumor-infiltrated lymphocytes, while they reduced the levels of myeloid-derived suppressor cells (MDSC) and suppressor T cells (Treg). We conclude that GNP-LLO91–99 nanovaccines can work as monotherapies or combinatory immunotherapies with anti-CTLA-4 or anti-PD-1 antibodies for solid tumors with high T cell infiltration, such as bladder cancer or melanoma.
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