ISOBIOTICS: Isotopic Labeling of Biotherapeutics

生物药物如肽、蛋白质、寡核苷酸和类似物为患者提供更有效和毒性更小的治疗，并且比化学药物具有更低的损耗率，因为进入临床试验的新生物实体中有1/9进入市场（化学药物为1/16）。因此，到2020年，24种最畅销的药物中有15种是生物治疗药物（世界市场份额约占每年1750亿美元收入的40%）。为了降低生物药物的免疫原性，克服其脆弱性并提高其快速和大规模到达其靶标的能力，广泛开发了尺寸减小的生物制剂。然而，通过接枝不显著改变其生物活性的双功能螯合剂来放射性标记大分子因此不再可能用于较小的生物药物。因此，至关重要的是设计新的放射性标记方法，在水介质和非常软的条件下进行微量。培训新一代放射化学家以实施这些方法并满足欧洲工业的需求也至关重要。ISOBIOTICS的目标：1）开发新的化学良性策略，用于用氘、氚和碳-14对大肽、小/中等大小蛋白质、寡核苷酸和类似物进行最后阶段放射性标记（临床前和0期临床评价）和氟-18（I-III期临床试验）; 2）通过跨学科实验室研究的结合，教育新一代年轻有才华的博士生，专门从事生物制剂的放射性标记，跨学科和跨部门借调、技术授课课程、科学讲座和补充技能讲习班; 3）确保所有ISOBIOTICS产出的适当传播、利用和交流，以最大限度地扩大项目的影响和辐射; 4）确保学生就业和培训结构的可持续性。

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.