
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: May 22, 2025
Abstract Glioblastoma remains a challenging indication for immunotherapy: the blood-brain barrier hampers accessibility systemic treatments and immunosuppressive microenvironment impedes immune attack. Intratumoral therapy with proinflammatory cytokine interleukin-12 (IL-12) can revert immunosuppression but leakage into circulation causes treatment-limiting toxicity. Here we engineer an IL-12Fc fusion reduced binding to neonatal Fc receptor FcRn. FcRn-silenced avoids FcRn-mediated brain export, thus exhibits prolonged retention blood levels, which prevents In murine glioblastoma, induces more durable responses negligible exposure boosts efficacy of radio- chemotherapy. It triggers anti-tumor independently peripheral T cell influx or lymphopenia leads inflammatory polarization tumor in patient-derived glioblastoma explants. FcRn-silencing may unlock full potential IL-12 cancer could be further applied containing activity other therapeutics targeting neurological diseases.
Language: Английский