HLA-homozygous iPSC-cardiomyocytE Aggregate manufacturing technoLogies for allogenic cell therapy to the heart (HEAL)

HLA-纯合 iPSC-心肌细胞 用于心脏同种异体细胞治疗 (HEAL) 的聚集体制造技术

• 批准号: 10039902
• 金额: $ 22.58万
• 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=10039902
• 关键词: HLA; homozygous; iPSC; cardiomyocytE; Aggregate

HEAL will focus on general bottlenecks to induced pluripotent stem cell therapies with a particular focus on heart failure, which remains a major cause of morbidity and mortality with very few treatment options. HLA-homozygous cell line derived cardiomyocyte aggregates offer the prospect of a restorative heart therapy applicable to large patient populations and to overcome economic barriers associated with autologous approaches. By developing solutions for their mass-production and cryopreservation we will enable allogeneic treatment with minimum requirements for immunosuppression. Assays for assessment of immunogenicity will provide data for the development of an artificial intelligence powered algorithm to predict recipients' immune responses for personalised design of immunosuppression protocols. A potency assay to assure product effectiveness will be developed together with assays of tumorigenicity in vitro and in vivo that meet and exceed current regulatory requirements. A genetic integrity pipeline defining the most sensitive assays for rigorous assessment will be developed and a rescue tool in the form of a biallelic suicide gene for programmed cell death will add to the safety toolbox for the therapy. Optimisation of cell-product administration in terms of retention and engraftment, including catheter-based delivery as minimally invasive alternative to surgical application, and assessment of risks of graft-induced arrhythmia will be determined in a pig model. Early dialogues, via established links, to the regulatory authorities will ensure proper development according to GMP requirements. Freedom to operate and licensing strategies with a health technology and infrastructure assessment of European centres will set the scene for approval of the cell product and related assays and protocols for storage and distribution required to progress towards a first in man study of cell-based heart repair.

HEAL将重点关注诱导多能干细胞治疗的一般瓶颈，特别关注心力衰竭，这仍然是发病率和死亡率的主要原因，治疗选择很少。hla纯合子细胞系衍生的心肌细胞聚集体提供了一种适用于大量患者群体的恢复性心脏治疗的前景，并克服了与自体方法相关的经济障碍。通过开发大规模生产和冷冻保存的解决方案，我们将实现对免疫抑制要求最低的同种异体治疗。评估免疫原性的试验将为人工智能算法的发展提供数据，以预测免疫抑制方案个性化设计的受体免疫反应。确保产品有效性的效价测定将与体外和体内致瘤性测定一起开发，以满足并超过当前的监管要求。将开发一个基因完整性管道，定义最敏感的严格评估分析，并以程序性细胞死亡的双等位基因自杀基因形式的救援工具将增加治疗的安全工具箱。优化细胞产物在保留和植入方面的给药，包括以导管为基础的给药作为手术应用的微创替代方案，以及评估移植物诱发心律失常的风险，将在猪模型中确定。通过与监管部门建立联系的早期对话将确保根据GMP要求进行适当的开发。对欧洲中心进行健康技术和基础设施评估的经营自由和许可战略，将为批准细胞产品以及相关的储存和分发分析和协议奠定基础，从而实现基于细胞的心脏修复的首次人体研究。