Gene-edited T cells combating IgA Nephropathy. A blueprint approach for safe & efficient genome editing of T cells to sustainably combat several immune diseases and cancers related to B-cell pathology

基因编辑 T 细胞对抗 IgA 肾病。

• 批准号: 10041031
• 金额: $ 137.95万
• 依托单位: UNIVERSITY OF OXFORD
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10041031
• 关键词: Gene; edited; cells; combating; IgA

There is an increasing prevalence of chronic diseases caused by undesired immune reactions (>10%) with high burden for the both patients (chronicity, organ failure, early death, decreased QoL) and society (EU:>100 bn €/a direct health costs) as current therapies are limited in efficacy and do not reshape sustainably the disturbed immune balance. Our ultimative goal is to develop a safe and efficient cell therapy based on genome-edited T cells with redirected specificity to sustainably combat IgA nephropathy (IgAN) - the most common glomerulonephritis and one of the most common causes of end-stage renal disease with unmet medical need. Our specific cell therapy approach is also suitable for other diseases with selective B-cell pathogenesis, such as IgA myeloma, IgA related celiac disease and rheumatoid arthritis, but as a blueprint also for diseases of other Ig classes (e.g. IgG4). Our novel concept offers a specific form of immunosuppression via Ig-(sub)class targeting & glycosylation targeting with redirected T cells in autoimmune diseases. Methodically, we benchmark three promising genome editing technologies, develop new standards for safety assessment and preclinical performance evaluation. At the end we will have a lead candidate of a new "living drug" product envisioned as a one-time treatment for IgAN and other IgA-associated that will be ready to enter clinical FIH trials (entry into TRL6). In addition, geneTIGA delivers enabling technology toolboxes with exploitation options beyond of the core project. They might de-risk and accelerate the development of next-generation gene and cell products in general. The project has thus, besides its scientific value, a high impact not only on the affected patients with IgAN and related immune diseases, but also for the European society by reducing the health economic burden caused by progressive chronic kidney disease, as well as by triggering innovation and business options in Europe's biotech and pharma field.

由于目前的治疗方法疗效有限，不能持续重塑被扰乱的免疫平衡，因此由非预期免疫反应（>10%）引起的慢性疾病的患病率日益增加，对患者（慢性病、器官衰竭、早死、生活质量下降）和社会（欧盟：> 1000亿欧元/a直接健康成本）造成了沉重负担。我们的最终目标是开发一种安全有效的细胞疗法，该疗法基于基因组编辑的T细胞，具有重定向特异性，可持续地对抗伊加肾病（IgAN）-最常见的肾小球肾炎，也是终末期肾病最常见的原因之一，医疗需求未得到满足。我们的特异性细胞治疗方法也适用于具有选择性B细胞发病机制的其他疾病，例如伊加骨髓瘤、伊加相关的乳糜泻和类风湿性关节炎，但也可作为其他IG类（例如IgG 4）疾病的蓝图。我们的新概念提供了一种特定形式的免疫抑制，通过IG-（亚）类靶向和糖基化靶向与重定向的T细胞在自身免疫性疾病。我们有条不紊地对三种有前途的基因组编辑技术进行基准测试，制定安全性评估和临床前性能评估的新标准。最后，我们将有一个新的“活药物”产品的主要候选人，设想作为IgAN和其他IgA相关的一次性治疗，将准备进入临床FIH试验（进入TRL 6）。此外，geneTIGA还提供了使能技术工具箱，其开发选项超出了核心项目。它们可能会降低风险，并加速下一代基因和细胞产品的开发。因此，除了其科学价值外，该项目不仅对IgAN和相关免疫疾病的患者产生了很大的影响，而且通过减少进行性慢性肾病造成的健康经济负担以及引发欧洲生物技术和制药领域的创新和商业选择，对欧洲社会也产生了很大的影响。