Detalle Publicación

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

Autores: Martinez Soldevilla, Mario; Villanueva, Helena; Meraviglia-Crivelli, Daniel ; Puravankara Menon, Ashwathi; Ruiz, Marta; Cebollero, Javier ; Villalba, María ; Moreno, Beatriz ; Lozano, Teresa; Llopiz, Diana; Pejenaute, Alvaro ; Sarobe Ugarriza, Pablo; Pastor, Fernando (Autor de correspondencia)
Título de la revista: MOLECULAR THERAPY
ISSN: 1525-0016
Volumen: 27
Número: 11
Páginas: 1878 - 1891
Fecha de publicación: 2019
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.