#IDIBELLfellows: Jose Luis Rocamora & Pau Fiol

ERK Signaling in Vascular Homeostasis: Therapeutic Implications for Hereditary Hemorrhagic Telangiectasia
Jose Luis Rocamora Navarro – Systemic, vascular diseases and ageing group
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disease characterized by vascular malformations. It is typically caused by mutations leading to ALK1 signaling haploinsufficiency during angiogenesis. This work demonstrates that ALK1 signaling downregulates ERK pathway, elucidating a new molecular mechanism in endothelial cells. Moreover, it reveals that HHT is associated to ERK signaling overactivation, proposing this pathway as a new therapeutical target for this disease with no curative treatment. In this line, in vivo experiments with clinically approved MEK inhibitors ameliorate HHT symptoms in mouse models.

Enhancing immune responses in cancer virotherapy: Oncolytic Adenoviruses Armed with a Bispecific T Cell Engager Targeting Folate Receptor Alpha for the Treatment of Ovarian Cancer
Pau Fiol Mata – Cancer immunotherapy group
Oncolytic adenoviruses (OAds) replicate in tumor cells and trigger immune responses, but clinical efficacy is limited. Bispecific T cell engagers (BsTEs) redirect T cells to tumors but have short half-life and toxicity. Combining OAds with BsTEs enhances efficacy: infected cells undergo oncolysis and release BsTEs, activating T cells locally. This study engineered ICOVIR15K to express a BsTE targeting folate receptor alpha (FRα). Although replication was slightly reduced, it maintained strong oncolytic activity and activated T cells in vitro. In mice, ICOVIR15K-FRαBsTE plus human T cells delayed tumor growth, showing promise for cancer immunovirotherapy.