Project description
Tiny synthetic antibody fragments as an alternative to monoclonal antibodies
Antibodies are proteins produced by the immune system that circulate in the bloodstream to fight infection by foreign ‘invaders.’ Monoclonal antibodies are synthetic antibodies that mimic the body’s natural ones. They hold great promise for the treatment of a plethora of diseases. However, they continue to face many challenges including long half-lives causing unwanted immune system activation and large size hindering their ability to leave the blood and enter tumours. With the support of the Marie Skłodowska-Curie Actions programme, the MirrorBody project will develop synthetic nanobodies, mimicking the smallest naturally derived antibody fragments with antigen-binding activity and shorter half-lives, to overcome these challenges.
Objective
The central role of molecularly-targeted therapeutics and imaging probes in translational research entails the development of an ever-growing arsenal of “chemical biologics” endowed with optimal in vivo properties. In this regard, mAbs and their derivatives (e.g. ADCs) still suffer from unsettled drawbacks involving difficulties in production and characterization, leading to heterogeneous conjugates in terms of size, potency and toxicity. Chemical modifications on mAbs are highly unreliable due to their complex structure: a central problem in this discipline, where heterogeneous drug-to-antibody ratio (DAR) and conjugation site represent significative limitations. Immunogenicity is a major drawback which affects humanized, as well as fully-human mAbs, and is exacerbated by long half-lives. Cases of unwanted activation of the immune system reportedly degenerated to life-threatening conditions such as acute anaphylaxis, serum sickness and cytokine release syndrome. Their bulky size (≈150 kDa) hinders their extravasation, impairing their efficiency to enter tumors.
Nanobodies (Nbs) are the smallest naturally-derived antibody fragments (≈13-14 kDa) that retain antigen-binding affinities in the same range of mAbs (nM to pM affinity range) while having extremely reduced half-lives ( ≈ 15 min.) when not bound to their target, thanks to a fast renal excretion.
MirrorBody intends to push the boundaries of targeted “chemical biologics” via an interdisciplinary approach that exploits both immunology and synthetic chemistry techniques for the generation of synthetic D-nanobodies that bind natural L-targets with high affinity. Such unprecedented synthetic D-Nbs will be endowed with improved biocompatibility, and will enable “plug-and-play” approaches for the controlled conjugation of diverse moieties.
Fields of science (EuroSciVoc)
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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)
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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.
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2021-PF-01
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75794 Paris
France
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