Improved engineering and manufacture of iPSC-derived CAR-NK cells for immunotherapy

改进用于免疫治疗的 iPSC 衍生 CAR-NK 细胞的工程设计和制造

• 批准号: 96212
• 金额: $ 17.54万
• 依托单位: PLASTICELL LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=96212
• 关键词: Improved; engineering; manufacture; iPSC; derived

Cancer is still a leading cause of death worldwide, and is thought to have been responsible for 9.6million deaths in 2018 (about 1 in 6 deaths). Unfortunately, despite improvements in cancer care and treatment, the incidence and the number of deaths from cancer are set to increase along with an aging and growing population. There is therefore a need for more effective treatments. Immunotherapy aims to boost the body's immune system to fight disease, and can be used to fight cancer. It uses substances made by the body or in a laboratory to improve how the body's immune system works to find and destroy cancer cells. Cellular immunotherapy is one type of immunotherapy that uses special blood cells of the immune system (T-cells or natural killer cells), and 'arms' them with the capacity to detect and destroy tumour cells. These so-called 'chimeric antigen receptor (CAR)-T' or 'CAR-NK' cells have revolutionised the treatment of patients with otherwise incurable cancers.However, these therapies have so far mostly relied on harvesting these blood cells from the patient or healthy donors. Whilst this method does work, it makes this therapeutic approach unpredictable, very expensive, and it requires a complex infrastructure for delivery. Another problem has been the development of adverse side effects in some patients with the use of CAR-T cell therapies. Therefore, any therapy that seeks to reduce variability, decrease cost, increase safety and make the manufacturing process faster and/or more robust, is hugely attractive. One such area of research is the use of 'induced pluripotent stem cells' (iPSCs). These cells can be made from adult tissue, and have the capacity to be cultured in the lab indefinitely and, more importantly, to give rise to any type of cell in the body - making them an ideal starting material for the manufacture of off-the-shelf cell therapies. They are also very amenable to genetic modification, which also makes them ideal for the 'arming' process mentioned above.There are two major aims of this project. The first is to deploy LambdaGen's advanced gene editing technology to arm iPSCs with multiple elements for enhanced capabilities for the detection and killing of tumour cells. The second is to deploy Plasticell's next generation screening technology to develop efficient methods to generate iPSC-derived natural killer cells. The combination of these two technologies promises to create an affordable, effective and safe therapy for the treatment of cancer.

癌症仍然是全球主要的死亡原因，被认为是2018年960万人死亡(约六分之一)的原因。不幸的是，尽管癌症护理和治疗有所改善，但随着人口老龄化和增长，癌症的发病率和死亡人数将会增加。因此，需要更有效的治疗方法。免疫疗法旨在增强人体的免疫系统以对抗疾病，并可用于对抗癌症。它使用由人体或实验室制造的物质来改善人体免疫系统发现和摧毁癌细胞的工作方式。细胞免疫疗法是一种免疫疗法，它使用免疫系统的特殊血细胞(T细胞或自然杀伤细胞)，并用检测和摧毁肿瘤细胞的能力来武装它们。这些所谓的“嵌合抗原受体(CAR)-T”或“CAR-NK”细胞使原本无法治愈的癌症患者的治疗发生了革命性变化。然而，到目前为止，这些治疗主要依赖于从患者或健康捐赠者身上采集这些血细胞。虽然这种方法确实有效，但它使这种治疗方法不可预测，非常昂贵，而且需要复杂的基础设施才能交付。另一个问题是使用CAR-T细胞疗法的一些患者会出现副作用。因此，任何寻求减少可变性、降低成本、提高安全性并使制造过程更快和/或更稳健的疗法都是非常有吸引力的。其中一个研究领域就是使用“诱导多能干细胞”(IPSCs)。这些细胞可以由成人组织制成，并具有在实验室无限期培养的能力，更重要的是，可以在体内产生任何类型的细胞-使它们成为制造现成细胞疗法的理想起始材料。它们也非常容易接受基因改造，这也使它们成为上述‘武装’过程的理想选择。这个项目有两个主要目标。首先是部署LambdaGen的先进基因编辑技术，为iPSCs配备多种元素，以增强检测和杀死肿瘤细胞的能力。第二个是部署Platticell的下一代筛选技术，以开发高效的方法来产生IPSC来源的自然杀伤细胞。这两项技术的结合有望创造出一种负担得起、有效和安全的癌症治疗方法。