Scientific publications

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

Nov 6, 2019 | Magazine: 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


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.

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

Our authors

Helena Villanueva Ruiz
Daniel Hackbrett Meraviglia-Crivelli de Caso
Dr. Marta Ruiz Egozcue
Research Technician Peptide Research Group
Investigadora del Programa de Terapias Moleculares del Cima Universidad de Navarra
Dr. Beatriz Moreno Bruna
Dr. Teresa Lozano Moreda
Researcher | Principal Investigator Immunology and Immunotherapy Research Program
Dr. Diana Llópiz Khatchikian