Project description
Personalised T cell therapy for brain tumours
Cancer cells express molecules on their surface that can potentially be recognised by the immune system. Selecting the most immunogenic epitopes of these antigens from the thousands of potential candidates present in each tumour remains challenging especially for brain tumours due to limited tissue access and sparse tumour-infiltrating T cells (TILs). The ERC-funded CENTRIC-BRAIN project shifts the focus from identifying tumour antigens to utilising existing, potentially effective T cell receptors (TCRs) from TILs. The project builds on predicTCR, a machine learning and AI-based system that can predict the tumour reactivity of TCRs and plans to use it to develop personalised adoptive cell therapies with engineered T cells.
Objective
Personalized tumor immunotherapy - vaccines and T cell therapies - requires the selection of few immunogenic epitopes recognized by tumor-reactive T cell receptors (TCRs) from thousands of potential tumor antigens in each tumor. This selection is a huge challenge, particularly in brain tumors, where access to tumor tissue is limited and tumor-infiltrating T cells (TILs) are sparse. CENTRIC-BRAIN will reverse this epitope-centric approach by directly harnessing tumor-reactive orphan TCRs from TILs for personalized brain tumor immunotherapy. Using human brain tumor tissue we have developed and experimentally validated predicTCR, a novel approach using machine learning and explainable AI to derive a classifier that predicts tumor-reactivity of such orphan TCRs based on the expression of signature genes with > 90% accuracy across multiple tumour entities. CENTRIC-BRAIN will employ predicTCR to develop a personalized adoptive cell therapy using transgenic T cells with tumor-specific TCRs and improved function.
CENTRIC-BRAIN hypothesizes that the signature genes underlying predicTCR determine the phenotypic and functional properties of tumor-reactive T cells and that predicted tumor-reactive orphan TCRs can be employed for adoptive therapy with personalized TCR-transgenic T cells.
Aim 1 will refine predicTCR by characterizing the transcriptional programs and spatial distribution of tumor-reactive T cells in human brain tumor samples. Aim 2 will define the functional relevance of transcriptional programs for tumor-reactive T cells in syngeneic humanized and patient-derived xenograft brain tumor models. Aim 3 will validate the predicted tumor-reactive orphan TCRs by adoptive transfer of T cells genetically engineered to express predicted tumor-reactive TCRs.
CENTRIC-BRAIN will thus revolutionize precise and efficient implementation of personalized adoptive cell therapy for brain tumors using T cells expressing tumor-reactive patient-derived orphan TCRs.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences basic medicine immunology immunotherapy
- medical and health sciences medical biotechnology cells technologies
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-ADG
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69120 Heidelberg
Germany
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