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ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a poss...

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Autores principales: Soldevilla, Mario Martínez, Villanueva, Helena, Meraviglia-Crivelli, Daniel, Menon, Ashwathi Puravankara, Ruiz, Marta, Cebollero, Javier, Villalba, María, Moreno, Beatriz, Lozano, Teresa, Llopiz, Diana, Pejenaute, Álvaro, Sarobe, Pablo, Pastor, Fernando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838990/
https://www.ncbi.nlm.nih.gov/pubmed/31405808
http://dx.doi.org/10.1016/j.ymthe.2019.07.013
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author Soldevilla, Mario Martínez
Villanueva, Helena
Meraviglia-Crivelli, Daniel
Menon, Ashwathi Puravankara
Ruiz, Marta
Cebollero, Javier
Villalba, María
Moreno, Beatriz
Lozano, Teresa
Llopiz, Diana
Pejenaute, Álvaro
Sarobe, Pablo
Pastor, Fernando
author_facet Soldevilla, Mario Martínez
Villanueva, Helena
Meraviglia-Crivelli, Daniel
Menon, Ashwathi Puravankara
Ruiz, Marta
Cebollero, Javier
Villalba, María
Moreno, Beatriz
Lozano, Teresa
Llopiz, Diana
Pejenaute, Álvaro
Sarobe, Pablo
Pastor, Fernando
author_sort Soldevilla, Mario Martínez
collection PubMed
description Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a possible target to include with CTLA-4 blocking treatment. Herein, we describe an ICOS agonistic aptamer that potentiates T cell activation and induces stronger antitumor responses when locally injected at the tumor site in combination with anti-CTLA-4 antibody in different tumor models. Furthermore, ICOS agonistic aptamer was engineered as a bi-specific tumor-targeting aptamer to reach any disseminated tumor lesions after systemic injection. Treatment with the bi-specific aptamer in combination with CTLA-4 blockade showed strong antitumor immunity, even in a melanoma tumor model where CTLA-4 treatment alone did not display any significant therapeutic benefit. Thus, this work provides strong support for the development of combinatorial therapies involving anti-CTLA-4 blockade and ICOS agonist tumor-targeting agents.
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spelling pubmed-68389902020-11-06 ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity Soldevilla, Mario Martínez Villanueva, Helena Meraviglia-Crivelli, Daniel Menon, Ashwathi Puravankara Ruiz, Marta Cebollero, Javier Villalba, María Moreno, Beatriz Lozano, Teresa Llopiz, Diana Pejenaute, Álvaro Sarobe, Pablo Pastor, Fernando Mol Ther Original Article Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there is still room for improvement in the quest for new therapeutic combinations. ICOS costimulation has been underscored as a possible target to include with CTLA-4 blocking treatment. Herein, we describe an ICOS agonistic aptamer that potentiates T cell activation and induces stronger antitumor responses when locally injected at the tumor site in combination with anti-CTLA-4 antibody in different tumor models. Furthermore, ICOS agonistic aptamer was engineered as a bi-specific tumor-targeting aptamer to reach any disseminated tumor lesions after systemic injection. Treatment with the bi-specific aptamer in combination with CTLA-4 blockade showed strong antitumor immunity, even in a melanoma tumor model where CTLA-4 treatment alone did not display any significant therapeutic benefit. Thus, this work provides strong support for the development of combinatorial therapies involving anti-CTLA-4 blockade and ICOS agonist tumor-targeting agents. American Society of Gene & Cell Therapy 2019-11-06 2019-07-25 /pmc/articles/PMC6838990/ /pubmed/31405808 http://dx.doi.org/10.1016/j.ymthe.2019.07.013 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Soldevilla, Mario Martínez
Villanueva, Helena
Meraviglia-Crivelli, Daniel
Menon, Ashwathi Puravankara
Ruiz, Marta
Cebollero, Javier
Villalba, María
Moreno, Beatriz
Lozano, Teresa
Llopiz, Diana
Pejenaute, Álvaro
Sarobe, Pablo
Pastor, Fernando
ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity
title ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity
title_full ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity
title_fullStr ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity
title_full_unstemmed ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity
title_short ICOS Costimulation at the Tumor Site in Combination with CTLA-4 Blockade Therapy Elicits Strong Tumor Immunity
title_sort icos costimulation at the tumor site in combination with ctla-4 blockade therapy elicits strong tumor immunity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838990/
https://www.ncbi.nlm.nih.gov/pubmed/31405808
http://dx.doi.org/10.1016/j.ymthe.2019.07.013
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