(327) Sphingomyelin-derived nanovesicles for the delivery epacadostat enhance melanoma immunotherapy

Introduction: Immune checkpoint blockade (ICB) therapy targeting CTLA-4 and PD-1/PD-L1 has shown promise in cancer treatment but benefits only a subset of patients. Combining ICB with inhibitors of immunosuppressive pathways, such as IDO1 inhibitors like epacadostat (EPA), aims to improve responses. EPA enhances T-cell activation and dendritic cell maturation, but its poor pharmacokinetics and tumor targeting limit efficacy. Here, we explore a sphingomyelin (SM)-based nanovesicle system, Epacasome, to enhance EPA delivery and synergize with anti-PD-1 therapy for better melanoma treatment outcomes.