New KRI preprint explores endothelin receptor blockade to enhance T cell-based immunotherapy

We are pleased to share a new preprint from researchers at KRI and collaborators, ‘Endothelin receptor blockade potentiates adoptive T cell and CAR T cell therapies,’ now available on bioRxiv.

The study investigates whether targeting the endothelin receptor pathway can improve the effectiveness of T cell-based cellular immunotherapies. Using preclinical models of triple-negative breast cancer and B-cell lymphoma, the work evaluates endothelin receptor blockade in combination with non-engineered adoptive T cell therapy and anti-CD19 CAR T cell therapy, with and without immune checkpoint inhibition.

Across both therapeutic approaches, endothelin receptor blockade increased tumour control responses, while its combination with immune checkpoint inhibition produced the most durable tumour control. Long-term responders also resisted tumour rechallenge, and high-dimensional profiling identified intratumoral T-cell states associated with tumour control, with elevated CD2 emerging as a recurring feature across these populations.

The findings support further investigation of the endothelin receptor pathway as a combinatorial strategy for enhancing T cell-based cellular immunotherapy.

The work was led by Charys Papagregoriou, with contributions from researchers at KRI and collaborating institutions, and senior authorship by Philippos Demetriou.