Publicaciones científicas

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

06-nov-2019 | Revista: Molecular Therapy

Mario Martínez Soldevilla, Helena Villanueva, Daniel Meraviglia-Crivelli, Ashwathi Puravankara Menon, Marta Ruiz, Javier Cebollero, María Villalba, Beatriz Moreno, Teresa Lozano, Diana Llopiz, Álvaro Pejenaute, Pablo Sarobe, Fernando Pastor


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.

CITA DEL ARTÍCULO  Mol Ther. 2019 Nov 6;27(11):1878-1891. doi: 10.1016/j.ymthe.2019.07.013. Epub 2019 Jul 25.

Nuestros autores

Helena Villanueva Ruiz
Técnico de Investigación Plataforma de Aptámeros y Química Médica
Daniel Hackbrett Meraviglia-Crivelli de Caso
Dra. Marta Ruiz Egozcue
Técnico de Investigación Grupo de Investigación en Péptidos
Investigadora del Programa de Terapias Moleculares del Cima Universidad de Navarra
Dra. Beatriz Moreno Bruna
Investigadora Adscrito a Proyecto Plataforma de Aptámeros y Química Médica
Dra. Teresa Lozano Moreda
Investigadora | Investigadora principal Programa de Investigación de Inmunología e Inmunoterapia
Dra. Diana Llópiz Khatchikian