Phase 1 SRN-101 intratumoral AAV–IFNβ immuno-gene therapy in recurrent high-grade glioma.

This first-in-human, single-arm, window-of-opportunity Phase 1 study tests SRN-101, an adeno-associated virus (AAV) gene therapy engineered to express interferon-beta (IFNβ) locally in tumor tissue, aiming to directly injure tumor cells while driving an inflamed, anti-tumor immune microenvironment. Participants with recurrent high-grade glioma who are already candidates for surgical resection receive a one-time intratumoral SRN-101 infusion via real-time MRI-guided convection-enhanced delivery (CED), then proceed to resection 7–21 days later to enable paired biologic readouts (tumor tissue plus blood-based pharmacology/immune effects). The trial uses a run-in dose (1.6E12 vector genomes) and a higher-dose cohort (5.0E12 vg) to establish early safety/tolerability and characterize local IFNβ expression and downstream immune activation. SRN-101 is associated with Siren Biotechnology’s AAV immuno-gene therapy program, while the listed sponsor is Nicholas Butowski at UCSF. For most recurrent high-grade glioma patients today, care is repeat surgery when feasible plus re-irradiation in selected cases and systemic options like temozolomide rechallenge, lomustine, and bevacizumab for symptom control—so this explores whether highly localized cytokine gene delivery can add a new lever beyond conventional cytotoxics and anti-VEGF therapy.