Project description
Advancing T cell therapy for solid tumours
Immunotherapy has reshaped how we treat cancer, but adoptive T cell therapies (ACTs) still face limited efficacy against solid tumours. This is due to the highly suppressive microenvironment that weakens T cell activity. With the support of the Marie Skłodowska-Curie Actions programme, the TLRT project aims to overcome that barrier by engineering T cells that can turn suppressive signals into activating ones. The idea is to reroute immune danger signals to boost T cell activity. By improving T cell strength and killing capacity, this approach could make ACTs far more effective across a broader range of solid tumours.
Objective
Immunotherapy, particularly adoptive T cell therapies (ACT), has revolutionized cancer treatment, providing significant benefits to patients with haematological malignancies. Despite these successes, their effectiveness against solid tumors remains limited. A major unaddressed obstacle in treating solid malignancies with ACT is the suppression of T cells within the tumor microenvironment (TME), which hampers their sustained activity against tumor cells. Thus, there is a critical need to optimize these therapies to be effective against a wider range of cancer types. One promising approach involves engineering adoptive T cells with switch receptors (SRs) that convert the detection of extracellular suppressive signals into intracellular T cell activation. Damage-associated molecular patterns (DAMPs) are endogenous ‘danger’ ligands and powerful innate immune agonists that signal through Toll-like receptors (TLRs) to various cell types, playing an essential role in mounting protective immunity. However, the potential to utilize these innate immune signals to empower therapeutic T cells remains unexplored. This research proposal aims to enhance ACT against solid tumors by leveraging innate immune signals to improve T cell function within the suppressive TME. Specifically, the goals are (1) to design innovative SRs that amplify TLR costimulatory signalling upon detecting TME immunosuppressive factors, and (2) to incorporate these SRs into T cells, evaluating their therapeutic potential in both TCR-T and CAR-T therapies using complementary murine and human tumor models. By harnessing innate inflammatory signals, the proposed strategy seeks to boost fitness, cytotoxicity, and resilience of infused T cells, enabling them to navigate and function more effectively within the immunosuppressive TME of solid tumors. The advancements from this research could be transformative for cancer treatment paradigms, offering new hope for a broader spectrum of cancer patients.
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
- 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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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.
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
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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2024-PF-01
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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.
80539 MUNCHEN
Germany
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.