FAST CAR-T: Faster, Adaptive and Scalable Technologies For CAR-T Manufacture

FAST CAR-T：更快、自适应和可扩展的 CAR-T 制造技术

• 批准号: EP/Z532770/1
• 负责人: Qasim Rafiq
• 金额: $ 254.84万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=EP%2FZ532770%2F1
• 关键词: FAST; CAR; Faster; Adaptive; Scalable

FAST CAR-T: Faster, Adaptive and Scalable Technologies for CAR-T ManufactureContext: Cell & gene therapies (CGTs) are transformative novel treatments which have demonstrated remarkable clinical outcomes. The most clinically and commercially advanced embodiment of CGTs are chimeric antigen receptor T (CAR-T) cellular immunotherapies. CAR-T therapy is a new type of personalised cancer treatment used to treat patients with blood cancers whose disease is resistant to chemotherapy and who have failed all other therapeutic options. CAR T cells can result in lasting remissions in patients with cancers previously considered incurable. Despite this clinical promise, CAR-T therapies can cost in excess of £300,000 due to the time and complexity of manufacture and the personalised nature of these therapies which introduce unprecedented challenges in their production and product release. Rapid, adaptive and scalable manufacturing solutions are required to reduce the cost of production, improve product consistency, and improve patient access to this transformative, curative therapeutic modality.Vision: Our vision is to revolutionise CAR-T production by delivering a step change in how CAR-T immunotherapies are developed and manufactured for both patient-specific therapies, and future universal donor CAR-T therapies. This will focus on addressing 3 key areas for future CAR-T manufacture: (1) make patient-specific CAR-T therapies faster (2) make the manufacturing process adaptive to accommodate patient variability, and (3) make it scalable to accommodate the next wave of allogeneic (universal donor) CAR-T therapies. This will be underpinned by a focus on the regulatory, operational and business models for decentralised, point-of-care manufacture.Overall Aim: We aim to establish a faster, more agile CAR-T production process for expedited manufacture and release and develop adaptive digital tools and scalable processes that enable the shift to autonomous manufacture with the associated controls needed for regulatory compliance to enable the decentralised production. Moreover, with the evolving science in the CAR-T sector, allogeneic (universal donor) CAR-T modalities are beginning to emerge. Allogeneic approaches involve the use of healthy donor T-cells, unlike autologous CAR T cell products, which are derived from individual patient samples and can be used in that individual patient only. Therefore, scalable manufacturing solutions are required for these future universal donor CAR-T production.This aim will be delivered through completion of four Work Packages (WPs):WP1: Development of a 2-day CAR-T manufacture process and implementation of an improved and expedited testing, release and certification of CAR-T products.WP2: Creation of digital tools, such as digital twins and process models, to enable autonomous, digitally-integrated, disruption-resilient CAR-T production.WP3: Development of scalable perfusion-based stirred-tank bioreactor process for universal donor CAR-T.WP4: Establishing the operational and business models, and regulatory environment for point-of-care CAR-T manufacture.Team: FAST CAR-T involves 8 investigators and 5 post-doctoral researchers across four different research and clinical organisations including UCL, Royal Free Hospital, University of Teesside and UWE Bristol. All academic partners are recognised leaders in their respective areas of research related to the FAST CAR-T proposal, specifically, CAR-T bioprocessing and GMP manufacture (UCL), biosystems analysis, digitalisation and control (Teesside), and redistributed manufacture and supply chain innovation (UWE). Through our collective and combined efforts, we believe we are ideally placed to deliver a comprehensive, cohesive and ambitious research programme, and deliver a step change in how CAR-T immunotherapies are developed and manufactured for both patient-specific therapies, and future universal donor CAR-T therapies.

FAST CAR-T：用于 CAR-T 制造的更快、适应性和可扩展的技术背景：细胞和基因疗法 (CGT) 是革命性的新型治疗方法，已显示出显着的临床效果，CGT 的临床和商业最先进的实施方案是嵌合抗原受体 T（ CAR-T）细胞免疫疗法是一种新型的个性化癌症治疗，用于治疗对化疗有抵抗力且所有其他疗法均无效的血癌患者。尽管有这样的临床前景，CAR-T 细胞可以使以前被认为无法治愈的癌症患者得到持久缓解，但由于制造的时间和复杂性以及这些疗法的个性化性质，CAR-T 疗法的成本可能超过 300,000 英镑。在生产和产品发布中引入前所未有的挑战，需要快速、适应性和可扩展的制造解决方案来降低生产成本，提高产品一致性，并改善患者获得这种变革性、治愈性治疗方式的机会。 愿景：我们的愿景是通过改变针对患者特异性疗法和未来通用供体 CAR-T 疗法的 CAR-T 免疫疗法的开发和制造方式，彻底改变 CAR-T 生产。这将重点解决未来 CAR-T 制造的 3 个关键领域。 ：（1）使患者特异性 CAR-T 疗法更快（2）使制造过程适应患者的变异性，（3）使其可扩展以适应下一波同种异体（通用供体）CAR-T 疗法。将重点关注分散式即时制造的监管、运营和商业模式。总体目标：我们的目标是建立更快、更灵活的 CAR-T 生产流程，以加快制造和发布，并开发自适应数字化技术工具和可扩展的流程，能够实现向自主制造的转变，并具有监管合规性所需的相关控制，以实现分散生产。此外，随着 CAR-T 领域科学的不断发展，同种异体（通用供体）CAR-T 已成为可能。与自体 CAR T 细胞产品不同，同种异体方法涉及使用健康的供体 T 细胞，自体 CAR T 细胞产品源自个体患者样本，并且只能用于该个体患者，因此需要可扩展的制造解决方案。这些未来的通用供体 CAR-T 生产。这一目标将通过完成四个工作包 (WP) 来实现：WP1：开发为期 2 天的 CAR-T 制造流程并实施改进和加速的测试、发布和实施CAR-T 产品认证。WP2：创建数字化工具，例如数字孪生和流程模型，以实现自主、数字集成、抗干扰的 CAR-T 生产。WP3：开发可扩展的基于灌注的搅拌罐生物反应器通用捐助者 CAR-T 的流程。WP4：建立床旁 CAR-T 制造的运营和商业模式以及监管环境。团队：FAST CAR-T 涉及 8 名研究人员和伦敦大学学院、皇家自由医院、蒂赛德大学和西英格兰大学布里斯托尔等四个不同研究和临床组织的 5 名博士后研究人员所有学术合作伙伴都是各自与 FAST CAR-T 提案相关的研究领域（特别是 CAR）的公认领导者。 -T 生物加工和 GMP 制造 (UCL)、生物系统分析、数字化和控制 (Teesside) 以及再分配制造和供应链创新 (UWE) 通过我们的集体和共同努力，我们相信我们是。非常适合提供全面、有凝聚力和雄心勃勃的研究计划，并为患者特异性疗法和未来通用供体 CAR-T 疗法的 CAR-T 免疫疗法的开发和制造方式带来重大改变。