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Browsing by Subject "onkolytiska adenovirus"

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  • Feodoroff, Michaela (2020)
    Within the field of cancer immunotherapy, immune checkpoint inhibitors have been a revolution since they provoke re-activation of T-cell immune responses towards cancer. Despite their success, they only work in 13% of the patients because of a poorly immunogenic tumor, mostly due to weak T-cell infiltration. Oncolytic viruses have shown the ability to work in synergy with checkpoint inhibitors because of their tumour-specific tropism, innate immunogenicity and ability to secrete immunostimulatory agents into the tumor microenvironment. Regardless of the great potential, we lack suitable pre-clinical models to test this effect. In this study we developed renal cell carcinoma-derived organoids as in vitro platforms due to their high pre-clinical predictability compared to that of murine and in vitro 2-dimensional cell culture models. To test the ability of oncolytic viruses to stimulate the immune system, we generated three cytokine-expressing (CXCL9, CXCL10 and IL-15) oncolytic adenoviruses using a novel cloning method that we developed. We have shown that these viruses successfully produce high amount of the cytokine and attract peripheral blood mononuclear cells freshly isolated from Buffy coats. Genetically modified oncolytic adenoviruses were also shown to infect and kill human renal cell carcinoma organoids. Together, our results demonstrate the potential of organoids as test platforms for oncolytic virus -based therapy and the importance of adequate cytokine expression in T-cell recruitment. The tumor organoid platform we developed will be useful for advancing patient-specific treatment strategies and serve as a base for innovative immunotherapy models.