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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Item Type: Tesi di dottorato
Lingua: English
Title: Novel adenoviral vaccine encoding multiple tumor neo-antigens in combination with checkpoint blockade as a strategy for more effective cancer treatment
Creators:
CreatorsEmail
De Lucia, Mariamariadelucia88@gmail.com
Date: 2018
Number of Pages: 77
Institution: Università degli Studi di Napoli Federico II
Department: dep14
Dottorato: phd054
Ciclo di dottorato: 30
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricovittorioenrico.avvedimento@unina.it
Tutor:
nomeemail
Nicosia, AlfredoUNSPECIFIED
Date: 2018
Number of Pages: 77
Uncontrolled Keywords: Adenoviral cancer vaccine, tumor neo-antigens, checkpoint blockade
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Date Deposited: 26 Dec 2017 16:38
Last Modified: 11 Apr 2019 10:35
URI: http://www.fedoa.unina.it/id/eprint/12048

Abstract

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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