Project description
New antibodies target tumour defences
Cancer immunotherapy is improving the outlook for many patients, but long-term success remains limited. Only a third of patients remain progression-free after five years. This is partly due to the presence of suppressive regulatory T cells (Tregs) in tumours, and standard antibodies struggle to penetrate and remain there. Supported by the Marie Skłodowska-Curie Actions programme, the ReTenTion project is creating new ICIs using smaller single-domain antibodies that target the 41-BB checkpoint on Tregs to block tumour-promoting cells while activating tumour-fighting T cells. By including a collagen-binding receptor, they remain longer in tumours, thereby improving retention and boosting the immune response. This approach offers a promising path toward more effective cancer treatments.
Objective
Immune checkpoint inhibitors (ICIs) for cancer therapy have revolutionized the treatment of several cancers. These ICIs are made from monoclonal antibodies that antagonize inhibitory signals via cytotoxic T-lymphocyte- associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) that block the tumoricidal activity of T cells. Although these ICIs have improved the overall survival of cancer patients such as cutaneous melanoma patients, only one third of patients has remained progression-free 5 years after initiating ICI therapy. This low efficacy is largely due to (1) the presence of immune suppressive regulatory T cells (Treg) within tumor microenvironment (TME) (2) the lack of efficacy of tumor penetration and retention. To improve the current ICI, this project RenTenTion aims to develop a next generation ICIs with smaller molecule so called single domain antibody (sdAb), give rise to enhanced tumor penetration. Targeting against a new immune checkpoint molecule 41-BB that highly expressed by intratumoral Treg, this next generation sdAb based ICI will inhibit tumor promoting immune cells Treg, while stimulate tumor rejecting immune cells such as effector T cells in tumors. Additionally, this project will couple the sdAb with collagen binding domain receptor so called leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) that bind to collagen in the tumor, therefore sustain tumor retention. This project “ReTenTion” will fill a gap for a strong need for new ICI molecules capable of addressing immunosuppressive in TME, yet smaller than conventional ICIs, boosting passive delivery.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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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)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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1050 Bruxelles / Brussel
Belgium
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