Project description
Enhancing immunotherapy for metastatic melanoma
Adoptive cell therapy (ACT) is an immunotherapy approach that involves engineering a patient’s immune cells, typically T cells, to enhance their ability to target and destroy cancer cells. This treatment has shown promise in cancers like melanoma, but faces challenges such as long production times, high costs and immune cell exhaustion within the tumour microenvironment. To enhance T cell immune cell fitness and sensitivity to immune checkpoint inhibitors, the ERC-funded NR2F6-AIM project will inhibit the NR2F6 transcription factor that acts as an intrinsic immune checkpoint in T cells. This means T cell activation and function is suppressed and therapeutic blockade of NR2F6 expression or function is likely to overcome the barriers posed by the immunosuppressive nature of the tumour microenvironment.
Objective
Melanoma cases and deaths are expected to increase in the coming years, representing a significant burden for the European economy and healthcare system. Metastatic melanoma (MM) is the most serious form of skin cancer and is characterised by uncontrolled metastatic spread of melanocytes to distant sites. Although standard treatments exist, significant clinical challenges remain, resulting in limited response and high MM recurrence rates. As a result of these limited treatment options, the quality of life of MM patients is dramatically compromised. Emerging immunotherapies, such as adoptive cell therapy (ACT), are promising but have significant obstacles, including long manufacturing times, high costs and, most critically, rapid exhaustion of infused cells due to the tumour immune microenvironment (TIME).
Research in Gottfried Baier's lab has identified a unique way to effectively stimulate the immune system with an ACT by inhibiting NR2F6, an intrinsic immune checkpoint of T lymphocytes. This is done through our NR2F6 blockade-based adoptive immune cell therapy for metastatic melanoma (NR2F6-AIM) approach, where T cells are engineered for enhanced immune fitness prior to infusion. This greatly sensitises the patient's immune system to currently available immune checkpoint inhibitor therapy (ICT). This approach will permit us to deliver a combinatorial treatment that can overcome TIME immunosuppression, providing curative potential against MM. NR2F6-AIM will block NR2F6 by a non-viral, time-boxed gene silencing through a synthetic small interfering RNA (siRNA) transfection method. This method will allow us to overcome therapeutic manufacturing hurdles through a one-day in-hospital preparation of the ACT. NR2F6-AIM will verify and optimise the technology in relevant in vivo and ex vivo study models to validate the potential of this innovative ACT. It will also develop and execute an IP strategy and a commercial feasibility analysis to enter the MM market.
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 clinical medicine oncology skin cancer melanoma
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine immunology immunotherapy
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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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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.
Funding Scheme
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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-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-POC
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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.
6020 INNSBRUCK
Austria
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.