De Lucia, Maria (2018) Novel adenoviral vaccine encoding multiple tumor neo-antigens in combination with checkpoint blockade as a strategy for more effective cancer treatment. [Tesi di dottorato]

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Cancer is a genetic disease initiated by somatic mutations that activate oncogenic drivers or inactivate onco-suppressor brakes. This genetic diversity from non-cancer cells can further increase, considering that tumor development is accompanied by the accumulation of further mutations that strengthen the divergence from a normal cell, making tumor cells more recognizable as foreign by the immune system. It has been demonstrated that the mutational burden of tumors contributes to immune recognition of cancer and it may influence response to cancer immunotherapy, such as immune checkpoints blockade. Neo-antigens are an important class of immunogenic tumor antigens and represent a promising target for vaccine therapy, having the potential to induce more robust and specific anti-cancer T cell responses than classical tumor-associated self-antigens. To exploit their immune potentiality for cancer immunotherapy, we developed a novel vaccine platform based on adenoviral vectors encoding multiple neo-antigens in tandem. Starting from the mutanome of the murine colon carcinoma cell line CT26, we selected thirty-one neo-antigens, identified as the more confident neo-antigen candidates, according to the applied prediction pipeline. Selected neo-antigens were inserted into a large adenovirus multi antigenic vaccine and tested in vivo for immunogenicity and efficacy in combination with checkpoint inhibitors.

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