SMARTCell: Scalable Manufacture of Advanced Regenerative Therapeutics - Cell Therapies

英国面临的最重大的医疗保健挑战是不可避免地向老年人过渡，人口老龄化，导致对医院和社会护理的需求增加，医疗干预复杂，成本不断上升，社会负担增加。因此，有必要开发新的、负担得起的和有效的药物，以确保我们保持和提高英国和全球医疗保健的标准。一种新型的药物，先进的细胞和基因治疗（CGT），最近已经成为一个有前途的治疗选择，以前无法治愈的条件。CGTs将成为下一代先进药物，有可能改善英国的健康和财富。CGT的实例包括细胞免疫疗法。这些药物使用基因工程细胞来靶向癌细胞。嵌合抗原受体自然杀伤细胞疗法（CAR-NK）是细胞免疫疗法的一个实例。自然杀伤细胞是一种关键的免疫细胞类型，可以对抗我们体内的感染，然而，我们可以通过基因工程改造它们来表达一种非天然蛋白质（CAR），这种蛋白质允许NK细胞靶向并消除血液癌细胞，这种能力是由于非天然CAR蛋白质才具备的。这些基因修饰疗法已经证明了显着的临床成功，并提供了一种革命性的方法来治疗那些其他治疗方案（例如化疗，骨髓移植）失败并最终注定死于疾病的患者。然而，这种新的治疗选择带来了戏剧性的结果，患者在接受治疗后多年完全缓解。它有效地治愈了癌症患者。然而，尽管它们的临床前景，批准的免疫疗法遭受高成本（> 350，000美元/剂），不明确的制造工艺和具有挑战性的基因工程方法，涉及使用昂贵和复杂的病毒作为基因递送的载体。如果没有重大的制造创新，这些变革性的治疗方法的承诺将无法实现，并且绝大多数需要它们的患者将无法获得它们。这对英国的健康、财富和福祉的影响是深远的。我的研究重点是建立一个可扩展的CAR-NK疗法的制造工艺，并展示CAR-NK细胞的第一升规模生产。这将通过创建创新和智能控制策略来实现，以改善生产过程并增加可制造的电池数量。我们将使用科学和工程方法来了解如何使细胞环境更有利于促进细胞生长，特别是监测和控制环境条件（例如气体，营养物质，温度，pH值）以支持最佳细胞生产。我们将建立生长和产生足够数量的细胞用于临床应用所需的工艺条件和技术。我们还将开发一种新的方法来设计细胞，这种方法不需要使用病毒（一种非病毒的方法），这是基于机械和化学方法。我的奖学金研究计划将支持工业和临床社区提供下一个-新一代的先进药物来治疗英国的患者，并确保这些治疗方法能够以合理的价格提供给需要它们的患者。英国卫生系统负担得起。这也将支持英国不断增长的细胞和基因治疗制造业的发展，并支持高增长生物制造业的经济活动。

The most significant healthcare challenge facing the UK is the unavoidable transition towards an older, ageing population, resulting in an increased demand for hospital and social care, complex medical interventions, spiralling costs and increased societal burden. The development of new, affordable and effective medicines will therefore be necessary to ensure we maintain and improve the standard of UK and global healthcare. A new type of medicine, advanced cell and gene therapy (CGT), has recently emerged as a promising treatment option for previously incurable conditions. CGTs will form the next-generation of advanced medicines with the potential to improve UK health and wealth. Examples of CGTs include cellular immunotherapies. These are medicines which use genetically-engineered cells to target cancer cells. Chimeric antigen receptor natural killer cell therapies (CAR-NK) are an example of a cellular immunotherapy. Natural killer cells are a key immune cell type that fights infections in our bodies, however, we can genetically-engineer them to express a non-native protein (the CAR) which allows the NK-cells to target and eliminate blood cancer cells, an ability they only possess because of the non-native CAR protein. These gene-modified therapies have demonstrated remarkable clinical success and offer a revolutionary approach to treat patients who have failed every other treatment option (e.g. chemotherapy, bone marrow transplant) and are ultimately destined to die of their disease. However, this new treatment option has resulted in dramatic outcomes, with patients in complete remission for years after receiving the therapy. It has effectively cured patients of their cancer. However, despite their clinical promise, approved immunotherapies suffer from high costs (>$350,000 per dose), poorly defined manufacturing processes and challenging gene engineering approaches involving the use of expensive and complex viruses as vehicles for gene delivery. Without significant manufacturing innovations, the promise of these transformative, curative therapies will not be realised, and they will remain inaccessible to the vast majority of patients that need them. The implications for UK health, wealth and well-being are profound. My Fellowship focuses on establishing a scalable manufacturing process for CAR-NK therapies and demonstrating the first litre-scale production for CAR-NK cells. This will be achieved by creating an innovative and intelligent control strategy to improve the production process and increase the number of cells that can be manufactured. We will use scientific and engineering approaches to understand how the cellular environment can be made more conducive to encourage cell growth, specifically monitoring and controlling the environmental conditions (e.g. gases, nutrients, temperature, pH) to support optimal cell production. We will establish the process conditions and technologies that are required to grow and generate sufficient numbers of cells for clinical applications. We will also develop a new way to engineer the cells using an approach that doesn't require the use of viruses (a non-viral approach) which is based on mechanical and chemical methods.My Fellowship research programme will support the industrial and clinical communities to deliver this next-generation of advanced medicines to treat patients in the UK and ensure these therapies are accessible to the patients that need them at a price that is affordable for the UK health system to bear. This will also support the development of the growing cell and gene therapy manufacturing industry in the UK and support economic activity in the high-growth biomanufacturing sector.