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：更快、自适应和可扩展的CAR-T治疗技术背景：细胞和基因疗法（CGT）是具有变革性的新型治疗方法，已证明具有显著的临床效果。CGT的临床和商业上最先进的实施方案是嵌合抗原受体T（CAR-T）细胞免疫疗法。CAR-T疗法是一种新型的个性化癌症治疗方法，用于治疗对化疗耐药且所有其他治疗方案均失败的血癌患者。CAR T细胞可以使以前被认为无法治愈的癌症患者获得持久的缓解。尽管有这种临床前景，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30万英镑，这给其生产和产品发布带来了前所未有的挑战。我们需要快速、自适应和可扩展的制造解决方案，以降低生产成本，提高产品一致性，并改善患者对这种变革性、治愈性治疗模式的使用。愿景：我们的愿景是彻底改变CAR-T免疫疗法的开发和制造方式，为患者特异性疗法和未来的通用供体CAR-T疗法带来革命性变化。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。总体目标：我们的目标是建立一个更快、更敏捷的CAR-T生产流程，以加快生产和发布，并开发自适应数字化工具和可扩展的流程，从而实现向自主生产的转变，并提供合规所需的相关控制，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模式开始出现。同种异体方法涉及使用健康供体T细胞，不像自体CAR T细胞产品，其来源于个体患者样品并且只能用于该个体患者。因此，未来的通用供体CAR-T生产需要可扩展的制造解决方案。这一目标将通过完成四个工作包（WP）来实现：WP 1：开发为期2天的CAR-T制造流程，并实施CAR-T产品的改进和加速测试、放行和认证。WP 2：创建数字化工具，如数字孪生和流程模型，以实现自主、数字集成、抗中断的CAR-T生产。WP 3：为通用供体CAR-T开发可扩展的基于灌注的搅拌罐生物反应器工艺。WP 4：为床旁CAR-T制造建立运营和商业模型以及监管环境。团队：FAST CAR-T涉及来自四个不同研究和临床组织的8名研究人员和5名博士后研究人员，包括UCL，皇家免费医院，提赛德大学和UWE布里斯托。所有学术合作伙伴都是与FAST CAR-T提案相关的各自研究领域的公认领导者，特别是CAR-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，我们相信我们处于理想的位置，可以提供一个全面，有凝聚力和雄心勃勃的研究计划，并在如何为患者特异性疗法和未来的通用供体CAR-T疗法开发和制造CAR-T免疫疗法方面实现一个飞跃。