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

FAST CAR-T: Faster, Adaptive and Scalable Technologies for CAR-T Manufacture Context: 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.