exTra_Innovative Applications of Extracorporeal Photopheresis in Solid Organ Transplantation

器官移植仍然是终末期心脏、肺、肝或肾疾病的唯一确定性治疗方法。早期移植结果现在通常很好，大大降低了患者的死亡率和发病率。然而，移植仍然面临着重大障碍，特别是长期免疫抑制相关毒性和移植功能的慢性下降，这是移植失败的主要原因。为了打破这些障碍，这在欧盟代表了非常重大的社会和经济负担，需要创新的疗法来减少我们对传统免疫抑制的依赖，并更好地控制非消退性炎症。体外光分离术（ECP）目前正在研究作为某些器官移植环境中的个性化辅助免疫抑制疗法。然而，ECP被认为是一种有争议的治疗方法，主要是因为目前对其药理作用的理解不完整，而且还因为最佳制造工艺，质量控制和个性化临床适应症仍然存在问题。exTra项目询问对ECP的更好的机械理解是否可以更有效地引导我们走向新的应用。具体而言，exTra汇集了欧洲临床移植、免疫学、药物开发、计算生物学和医疗器械制造方面的专家，通过协调的跨学科努力解决关键问题。exTra提出了10个独立的博士研究项目，其目标是为学员提供对基础和转化免疫学的全面了解，特别是与新免疫疗法的开发和许可有关的知识。通过其研究和培训活动，exTra项目将为欧洲的科学进步和创新做出贡献，最终从移植免疫治疗及其他领域的临床创新中产生社会和经济效益。

Organ transplantation remains the only definitive treatment for end-stage heart, lung, liver or kidney disease. Early transplant outcomes are now generally excellent, dramatically reducing patients' mortality and morbidity. Nevertheless, transplantation still faces significant obstacles, especially long-term immunosuppression-related toxicity and chronic decline of transplant function, which are the leading causes of transplant failure. To break these barriers, which represent a very significant societal and economic burden in the EU, there is a need for innovative therapies to lessen our reliance on conventional immunosuppression and better control non-resolving inflammation. Extracorporeal photopheresis (ECP) is now being investigated as a personalized, adjunct immunosuppressive therapy in some organ transplant settings. However, ECP is regarded as a controversial therapy, primarily because current understanding of its pharmacological actions is incomplete, but also because there remain questions about optimal manufacturing processes, quality-control and personalized clinical indications. The exTra project asks whether a better mechanistic understanding of ECP can guide us more efficiently towards novel applications. Specifically, exTra brings together European experts in clinical transplantation, immunology, pharmaceutical development, computational biology and medical device manufacture to address key questions through a coordinated, interdisciplinary effort. exTra proposes 10 independent doctoral research projects with the ambition of providing its trainees with a comprehensive understanding of basic and translational immunology, especially relating development and licensing of new immunotherapies. Through its research and training activities, the exTra project will contribute to scientific advancement and innovation in Europe, ultimately leading to societal and economic benefits stemming from clinical innovations in transplant immunotherapy and beyond.