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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Authors: Martínez-Soldevilla, M. (Mario)|||/items/6803c2fb-2204-4c18-b86b-ea7f08a42f99, Villanueva-Ruiz, H. (Helena)|||/items/3f124623-46bb-46f8-9f0e-892430b05393, Meraviglia-Crivelli, D. (Daniel)|||/items/b902e660-09d8-4cbd-be91-603810f3c23e, Menon, A.P. (Ashwathi Puravankara)|||/items/764fd0e3-e40e-40f5-91dc-44c9e09e3966, Ruiz, M. (Marta)|||/items/527b5812-5743-432f-8025-d5c0df943270, Cebollero, J. (Javier)|||/items/4b6cf99a-a094-43d3-b9fa-825cf9e60165, Villalba, M. (María)|||/items/7f65b092-d480-4953-a790-65baf0bb567d, Moreno-Bruna, B. (Beatriz)|||/items/0fc554b7-0d6a-4acf-a866-69c040c3419f, Lozano-Moreda, T. (Teresa)|||/items/f7df715d-1380-479b-8134-b319df8f0b00, Llopiz-Khatchikian, D.I. (Diana Isabel)|||/items/3b1cd705-ce8b-4f99-b323-460f59b34f20, Pejenaute-Martínez-de-Lizarrondo, Á. (Álvaro)|||/items/f10e17ed-8b4e-4d5c-8985-3f73a691f9d0, Sarobe, P. (Pablo)|||/items/e6f6a7ac-cfe2-409e-ab14-057dea5fd160, Pastor-Rodríguez, F. (Fernando)|||/items/b59e53ff-7114-4575-b185-f66ca445890b
Format: article
Publication Date:2019
Country:España
Institution:Universidad de Navarra
Repository:Dadun. Depósito Académico Digital de la Universidad de Navarra
Language:English
OAI Identifier:oai:dadun.unav.edu:10171/62974
Online Access:https://hdl.handle.net/10171/62974
Access Level:Open access
Keyword:Target therapeutics
Cancer immunotherapy
ICOS
CTLA-4
Aptamer
Description
Summary: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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