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A novel immuno-oncolytic virus-based dendritic cell therapeutic cancer vaccine

Project description

Oncolytic virus releases immunogenic lysate leading to personalised vaccines

Dendritic cells are a heterogeneous group of innate immune cells that induce adaptive immune responses to cancer. They retrieve, process and present tumour-derived antigens to naive T cells, thereby activating them. DC-based vaccines could be particularly potent via such induced systemic immune responses. Despite their potential, they have had limited clinical efficacy, in part due to the inability to sufficiently mature DC cells and the difficulty selecting optimal tumour antigens. The ERC-funded DCanVAX project aims to develop a mechanism for DC maturation and activation and use a virus to lyse tumour cells ex-vivo, releasing all tumour antigens as well as markers of virus infection. It could lead to personalised DC-based vaccine generation.

Objective

Following decades of development, therapeutic cancer vaccines are beginning to gain momentum in demonstrating therapeutic effects, and they represent a particularly promising approach. The aim of therapeutic cancer vaccines is to stimulate immunity against tumor antigens, usually through the use of whole cells, peptides, or nucleic acids (i.e. mRNAs). Dendritic cell- (DC) based vaccines represent particularly interesting candidates for therapeutic cancer vaccine products due to their ability to cross-present antigens to T cells, thereby driving adaptive immune responses through induction of antigen-specific cytotoxic T lymphocytes. Despite the potential of DC-based cancer vaccines, several major limitations have hindered their success in clinical studies. These limitations include insufficient ex vivo maturation of DCs and challenges in selecting optimal tumor antigens to target. The aim of DCanVAX is to develop a novel oncolytic virus-based dendritic cell vaccine approach for systemic therapy of solid cancers. We propose that the use of a highly immuno-oncolytic virus as a mechanism to lyse tumor cells ex-vivo, will lead to the release of the entire tumor antigen library, as well as a cocktail of danger signals in response to the virus infection. By applying this highly immunogenic lysate to autologous DCs, an optimized and personalized DC vaccine can be generated. This method overcomes the major challenges that have been encountered by DC vaccine approaches in the clinic, by providing a potent mechanism of DC maturation and activation, while simultaneously exposing the DCs to the complete repertoire of tumor antigens that are specific to the patient, leading to potent and broad tumor-specific immune responses against the cancer. This approach can be developed for multiple solid cancer indications and combined with other immunotherapy approaches for potentially synergistic therapeutic effects.

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2023-POC

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Host institution

KLINIKUM DER TECHNISCHEN UNIVERSITÄT MÜNCHEN (TUM KLINIKUM)
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
ISMANINGER STRASSE 22
81675 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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