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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/175693
Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency
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[eng] The general goal of this thesis has been to progress oncolytic adenovirus therapy for PDAC, by the incorporation of novel preclinical models to test for patient-specific responses and the generation of oncolytic adenoviruses with enhanced therapeutic index. The two main objectives have been the following: i) Evaluate patients-derived organoids (PDOs) technology as a platform to screen for personalized virotherapy in vitro 1) Establishment of a battery of PDOs from PDAC and normal pancreatic tissues, and evaluation of their applicability in the study of adenoviral infection; 2) Screening of a battery of PDOs to identify individual sensitivities to virotherapies, and the effects derived from the combination with chemotherapy; 3) Study virotherapy-responses in metastasis originated from PDOs xenografted in mice; (ii) Improve oncolytic adenovirus potency by modulation of miRNAs deregulated in PDAC 4) Screening of aberrantly expressed miRNAs sensitizing viral oncolysis in PDAC via CRISPR/Cas9 system; 5) Generation of a miRNA sponge-adenovirus and evaluation of its oncolytic effects in vitro and in vivo; 6) Modulation of miRNA levels with the THZ1 transcriptional inhibitor, and assessment of the effects of its combination with oncolytic adenoviruses.
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RAIMONDI, Giulia. Broadening Adenoviral Oncolysis in PDAC: Interrogation of Patient-Derived Organoids for personalized virotherapy and modulation of miRNA content to boost adenoviral potency. [consulted: 10 of August of 2026]. Available at: https://hdl.handle.net/2445/175693