ISOBIOTICS: Isotopic Labeling of Biotherapeutics

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Biological drugs such as peptides, proteins, oligonucleotides and analogs provide the patients with more efficacious and less toxic treatments and have lower attrition rates than chemical drugs since 1 on 9 new biological entities entering clinical trials reaches the market (1 on 16 for chemical drugs). Consequently, 15 on 24 top blockbuster drugs were biotherapeutics in 2020 (world-market share of about 40% of $175 billion of revenue per year). In order to reduce the immunogenicity of biodrugs, to overcome their fragility and to increase their capacity to reach quickly and massively their target, reduced-size biologics are extensively developed. However, radiolabeling of large molecules by grafting bifunctional chelating agents which do not alter significantly their biological activity is thus no longer possible with smaller biodrugs. It is therefore of paramount importance to devise new radiolabeling approaches carried out on tiny quantities in aqueous media and very soft conditions. It is also crucial to train a new generation of radiochemists in order to implement these methods and to meet the needs of the European industry. ISOBIOTICS ambitions: 1) to develop new chemically-benign strategies for the last-stage radiolabeling of large peptides, small/medium-size proteins, oligonucleotides and analogs with deuterium, tritium and carbon-14 (preclinical and phase 0 clinical evaluation), and fluorine-18 (phase I-III clinical trials); 2) to educate a new generation of young talented PhD students specialized in the radiolabeling of biologics through a combination of interdisciplinary lab research, transdisciplinary and intersectorial secondments, technical taught courses, scientific lectures and complementary skills workshops; 3) to ensure the appropriate dissemination, exploitation and communication of all ISOBIOTICS outputs in order to maximize the project's impact and radiance; 4) to secure the students employment and the sustainability of training structures.