Preclinical development of an extracellular vesicle biotherapeutic for juvenile idiopathic arthritis

幼年特发性关节炎细胞外囊泡生物治疗药物的临床前开发

• 批准号: 10068495
• 金额: $ 123.45万
• 依托单位: MESENBIO LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10068495
• 关键词: Preclinical; development; extracellular; vesicle; biotherapeutic

Mesenbio's aim is to accelerate the clinical development of extracellular vesicle (EV) biotherapeutics. We have engineered a human mesenchymal stem cell line to produce a limitless, consistent supply EVs with intrinsic anti-inflammatory and tissue regenerating properties. Our intention is to develop these EVs as a disruptive new therapy for inflammatory arthritis, with refractory juvenile idiopathic arthritis (JIA) as our initial target indication.EVs are nano-sized, membrane-bound structures containing biological material, including nucleic acids and proteins. EVs are released by cells to deliver their bioactive cargoes and elicit functional change in target cells (e.g. growth, differentiation, immune suppression). Therefore EVs are increasingly viewed as an exciting new biotherapeutic paradigm, uncomplicated by the problems associated with cellular therapies, such as immune-compatibility, survival, storage, transport and costs. The key challenges for bringing EV therapies to market are consistency, efficacy and scale-up, which all link back to the source and supply of the EV-producing cells, which cannot rely on the constant sampling of uncharacterised donated human cells of variable quality and quantity.In 2010, we initiated a programme of work to identify authentic mesenchymal stem cells (MSCs) within a mixed population of human bone marrow stromal cells. Heterogeneous stromal cells were immortalised and expanded as single cell-derived colonies. The immortalised status enabled in-depth characterisation of many clones over several years and we succeeded in identifying clone Y201, which has the marker profile, morphological features and all the differentiation and immunosuppressive characteristics of true MSCs (James S. et al, Stem Cell Reports, 2015; Kay AG et al, Front. Immunol., 06 June 2022). We have demonstrated that Y201 MSCs produce a continuous, consistent supply of EVs that have both immunosuppressive and tissue-forming capabilities. In 2021 we founded the company, Mesenbio, to accelerate the development of Y201 EVs as a production platform to treat inflammatory joint disease, with refractory JIA as our first clinical target.The aim of this proposal is to advance the preclinical development of Y201 EVs to support regulatory approval for first-in-human clinical trials. We will focus here on upstream processing, characterisation and safety and efficacy of the EV product with the aim of attracting further funding to progress the therapy to clinical trial application.

梅森比奥的目标是加速细胞外小泡(EV)生物疗法的临床开发。我们已经设计出一种人类间充质干细胞系，以产生无限、一致的供应具有内在抗炎和组织再生特性的EVS。我们的目的是开发这些EVS作为一种治疗炎症性关节炎的颠覆性新疗法，以难治性幼年特发性关节炎(JIA)为初始目标指标。EVS是纳米尺寸的膜结合结构，包含生物材料，包括核酸和蛋白质。EV是由细胞释放的生物活性物质，并引起靶细胞的功能变化(如生长、分化、免疫抑制)。因此，电动汽车越来越被视为一种令人兴奋的新生物治疗范式，不会因细胞治疗相关的问题而复杂化，如免疫兼容性、生存、储存、运输和成本。将EV疗法推向市场的关键挑战是一致性、有效性和规模化，这些都与EV产生细胞的来源和供应有关，而EV产生细胞的来源和供应不能依赖于对不同质量和数量的未鉴定捐赠人类细胞的持续采样。2010年，我们启动了一项工作计划，在人类骨髓基质细胞的混合群体中识别真正的间充质干细胞(MSCs)。异种基质细胞被永生化并作为单个细胞来源的克隆扩增。永生化状态使我们能够在几年内对许多克隆进行深入的鉴定，我们成功地鉴定了克隆Y201，它具有真正MSCs的标记特征、形态特征和所有分化和免疫抑制特征(James S.等人，Stem Cell Reports，2015；Kay AG等人，Front)。免疫。2022年6月6日)。我们已经证明，Y201年的MSCs产生持续、一致的EV供应，具有免疫抑制和组织形成能力。2021年，我们成立了梅森比奥公司，以加快Y201 EVS的开发，将其作为治疗炎症性关节疾病的生产平台，将难治性JIA作为我们的第一个临床目标。这项提议的目的是推进Y201 EVS的临床前开发，以支持监管机构批准进行首例人类临床试验。我们在这里将重点放在EV产品的上游工艺、特性以及安全性和有效性上，目的是吸引更多资金将该疗法推向临床试验应用。