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An integrative genetic approach for the exploration of melanoma immunological interactions

Objective

Immunotherapy, which has revolutionized cancer treatment, largely relies on the immune system’s recognition of neopeptides, degradation products of altered proteins specific to cancer cells presented on their surface. In particular, cancer vaccines targeting neopeptides have shown promising clinical results. Yet, to optimize their efficacy and broaden their application, we need to decipher the nature of the cancer peptide landscape (immunopeptidome) and delineate the neopeptide properties required to induce a potent immune response. The overarching goal of this proposal is to provide an unprecedented, thorough, multifaceted understanding of the mechanisms underlying aberrant peptide production, peptide-MHC presentation, and T-cell recognition in melanoma. We will do so by pursuing three key avenues: Systematic interrogation of the cancer immunopeptidome to identify novel canonical and non-canonical cancer antigens and quantify their presentation (Aim 1). Comprehensive functional assessment of the intrinsic qualities of actionable antigens by quantitatively charting the immunopeptidome in-vivo, while considering peptide presentation levels, clonality and cross-presentation; and delineating how these neoantigen qualities impact the immune response (Aim 2). Establish controlled in-vivo models to tease apart neoantigen qualities for the establishment of rational cancer vaccine modalities (Aim 3). In this effort, we will draw upon our pioneering tools and advanced mapping of the cancer peptidome in melanoma, which has already revealed novel antigenic sources. Our research approach combines comprehensive quantitative immunopeptidomics, novel imaging and computational approaches, advanced functional assays and novel mouse models. Our project will provide a fresh view of melanoma-immune interactions, new research tools and pipelines, cancer-specific antigen targets for immunotherapy and, more broadly, a paradigm for addressing similarly complex questions in other cancers.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2022-ADG

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Host institution

WEIZMANN INSTITUTE OF SCIENCE
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.

€ 2 500 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 500 000,00

Beneficiaries (1)

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