EXODUS-BCL (Exosome-Delivered PROTAC to Overcome Therapeutic Resistance in Aggressive B-Cell Lymphome)

The project aims to develop an innovative therapeutic strategy for aggressive B-cell lymphomas by using exosome-delivered dual ligand PROTACs. The general objective is to simultaneously overcome therapeutic resistance and reprogram the immunosuppressive tumor microenvironment (TME), thereby improving treatment efficacy and patient outcomes in diseases such as diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Urgent need to address limitations of current therapies.

First, therapeutic resistance remains a major cause of treatment failure, reducing survival rates. Dual ligand PROTACs, a novel class of protein-degrading drugs, offer a way to selectively eliminate resistance-driving proteins. Second, the immunosuppressive TME characteristic of these lymphomas prevents effective immune responses; reprogramming this environment can restore immune surveillance. Finally, exosomes provide an advanced drug delivery platform, ensuring targeted action, better bioavailability, and reduced systemic toxicity.

The central hypothesis is that exosome-delivered dual ligand PROTACs can both counteract resistance and reprogram the TME to enhance anti-tumor immunity, ultimately improving therapeutic outcomes. This project, funded by the Agencia Estatal de Investigación (AEI) 2024 Call – “Proyectos de Generación de Conocimiento, Ref. PID2024-160983OB-C22”, is carried out in collaboration between the Josep Carreras Institute (IJC) and Institut Químic de Sarrià (IQS).