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AAV-iIL12 is an adeno-associated virus (AAV) gene therapy vector designed for the localized, inducible expression of Interleukin-12 (IL-12) within the tumor microenvironment. Developed by researchers at Cima-Universidad de Navarra, the platform utilizes an interferon (IFN)-inducible promoter to drive IL-12 expression, specifically leveraging the type-I IFN produced via the cGAS-STING pathway following ionizing radiation (radiotherapy). This spatial and temporal control aims to minimize systemic toxicity associated with IL-12 while remodeling the tumor microenvironment to activate potent innate and adaptive antitumor immunity. Preclinical studies demonstrate that radiotherapy enhances AAV transduction through epigenetic remodeling of vector episomes and recruitment of the transcription factor YY1, leading to synergistic efficacy in various tumor models.
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