ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity
Keywords: 
Target therapeutics
Cancer immunotherapy
ICOS
CTLA-4
Aptamer
Issue Date: 
2019
Publisher: 
Elsevier BV
ISSN: 
1525-0016
Note: 
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Citation: 
Martínez-Soldevilla, M. (Mario); Villanueva, H. (Helena); Meraviglia-Crivelli, D. (Daniel); et al. "ICOS costimulation at the tumor site in combination with CTLA-4 blockade therapy elicits strong tumor immunity". Molecular Therapy. 27 (11), 2019, 1878 - 1891
Abstract
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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