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STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity

Combining different immunotherapy approaches is currently building the future of immunotherapy, with the view to maximize anti-tumoral efficacy for larger patient population. The KISIMA™ platform allows the development of protein-based cancer vaccines able to induce tumor-specific T cell response re...

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Autores principales: Rossi, Matteo, Carboni, Susanna, Di Berardino-Besson, Wilma, Riva, Erika, Santiago-Raber, Marie-Laure, Belnoue, Elodie, Derouazi, Madiha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283310/
https://www.ncbi.nlm.nih.gov/pubmed/34276686
http://dx.doi.org/10.3389/fimmu.2021.695056
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author Rossi, Matteo
Carboni, Susanna
Di Berardino-Besson, Wilma
Riva, Erika
Santiago-Raber, Marie-Laure
Belnoue, Elodie
Derouazi, Madiha
author_facet Rossi, Matteo
Carboni, Susanna
Di Berardino-Besson, Wilma
Riva, Erika
Santiago-Raber, Marie-Laure
Belnoue, Elodie
Derouazi, Madiha
author_sort Rossi, Matteo
collection PubMed
description Combining different immunotherapy approaches is currently building the future of immunotherapy, with the view to maximize anti-tumoral efficacy for larger patient population. The KISIMA™ platform allows the development of protein-based cancer vaccines able to induce tumor-specific T cell response resulting in anti-tumoral efficacy in various mouse models. Intra-tumoral administration of stimulator of interferon gene agonists (STINGa) was shown to induce a potent inflammatory response leading to the development of tumor-specific immunity. Here, we explored the efficacy and mechanisms of action of subcutaneous STINGa treatment combined with therapeutic vaccination in various mouse tumor models. This combinatory treatment highly enhanced frequency and effector function of both peripheral and intra-tumoral antigen-specific CD8 T cells, promoting potent IFNγ and TNFα production along with increased cytotoxicity. Moreover, combination therapy favorably modulated the tumor microenvironment by dampening immune-suppressive cells and increasing CD4 T cell infiltration together with their polarization toward Th1 phenotype. Combination with STINGa treatment improved the effect of therapeutic vaccination, resulting in a prolonged control and slower growth of B16-OVA and TC-1 tumors. Altogether, the results presented here highlight the potential of combining STINGa with a therapeutic protein vaccine for cancer treatment.
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spelling pubmed-82833102021-07-17 STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity Rossi, Matteo Carboni, Susanna Di Berardino-Besson, Wilma Riva, Erika Santiago-Raber, Marie-Laure Belnoue, Elodie Derouazi, Madiha Front Immunol Immunology Combining different immunotherapy approaches is currently building the future of immunotherapy, with the view to maximize anti-tumoral efficacy for larger patient population. The KISIMA™ platform allows the development of protein-based cancer vaccines able to induce tumor-specific T cell response resulting in anti-tumoral efficacy in various mouse models. Intra-tumoral administration of stimulator of interferon gene agonists (STINGa) was shown to induce a potent inflammatory response leading to the development of tumor-specific immunity. Here, we explored the efficacy and mechanisms of action of subcutaneous STINGa treatment combined with therapeutic vaccination in various mouse tumor models. This combinatory treatment highly enhanced frequency and effector function of both peripheral and intra-tumoral antigen-specific CD8 T cells, promoting potent IFNγ and TNFα production along with increased cytotoxicity. Moreover, combination therapy favorably modulated the tumor microenvironment by dampening immune-suppressive cells and increasing CD4 T cell infiltration together with their polarization toward Th1 phenotype. Combination with STINGa treatment improved the effect of therapeutic vaccination, resulting in a prolonged control and slower growth of B16-OVA and TC-1 tumors. Altogether, the results presented here highlight the potential of combining STINGa with a therapeutic protein vaccine for cancer treatment. Frontiers Media S.A. 2021-07-01 /pmc/articles/PMC8283310/ /pubmed/34276686 http://dx.doi.org/10.3389/fimmu.2021.695056 Text en Copyright © 2021 Rossi, Carboni, Di Berardino-Besson, Riva, Santiago-Raber, Belnoue and Derouazi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Rossi, Matteo
Carboni, Susanna
Di Berardino-Besson, Wilma
Riva, Erika
Santiago-Raber, Marie-Laure
Belnoue, Elodie
Derouazi, Madiha
STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity
title STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity
title_full STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity
title_fullStr STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity
title_full_unstemmed STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity
title_short STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity
title_sort sting agonist combined to a protein-based cancer vaccine potentiates peripheral and intra-tumoral t cell immunity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283310/
https://www.ncbi.nlm.nih.gov/pubmed/34276686
http://dx.doi.org/10.3389/fimmu.2021.695056
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