Project description
A ‘tweaking’ strategy for T lymphocytes according to the clinical needs
Adoptive T-cell therapy is a revolutionary approach in various clinical interventions, including target-specific cancer immunotherapy and fighting chronic infections, auto-immunity and undesired immune responses after organ transplantation. Currently, its clinical applications are complicated by the acquisition of senescence during the in vitro T-cell expansion phase, and by the functional plasticity of T cells which after transfusion may result in a functional switch from the desired effect. Epigenetic players such as DNA methylation contribute to T-cell differentiation, creating a unique possibility to stabilise the development and function of cells. The EU-funded EpiTune project aims to equip T lymphocytes with properties that would guarantee their successful and safe therapeutic application, including their functional fine-tuning according to the clinical needs. The idea is to improve T-cell therapy by directed modifications of the epigenome.
Objective
"Adoptive T cell therapy is a promising approach in various clinical settings, from target-specific immune reconstitution fighting cancer and chronic infections to combating undesired immune reactivity during auto-immunity and after organ transplantation.
However, its clinical application is currently hampered by: 1) the acquisition of senescence during the required in vitro expansion phase of T cells which limits their survival and fitness after infusion into the patient, and 2) the functional plasticity of T cells, which is sensitive to the inflammatory environment they encounter after transfusion and which might result in a functional switch from the desired effect (e.g. immunosuppressive) to the opposite one (pro-inflammatory).
I want to tackle these obstacles from a new molecular angle, utilizing the profound impact of epigenetic mechanisms on the senescence process as well as on the functional imprinting of T lymphocytes. Epigenetic players such as DNA methylation essentially contribute to T cell differentiation and harbor the unique prospect to imprint a stable developmental and functional state in the genomic structure of a cell, as we could recently show in our basic immune-epigenetic studies. Therefore, I here propose to equip T lymphocytes with the required properties for their successful and safe therapeutic application, including their functional fine-tuning according to the clinical need by directed modifications of the epigenome
('Epi-tuning').
To reach these goals I want: 1) to reveal strategies for the directed manipulation of the epigenetically-driven mechanism of cellular senescence and 2) to apply state-of-the-art CRISPR/Cas9-mediated epigenetic editing approaches for the imprinting of a desired functional state of therapeutic T cell products. These innovative epigenetic ""one-shot"" manipulations during the in vitro expansion phase should advance T cell therapy towards improved efficiency, stability as well as safety."
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.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics epigenetics epigenomes
- medical and health sciences clinical medicine transplantation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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.
ERC-STG - Starting Grant
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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-2018-STG
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10117 Berlin
Germany
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