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

癌症仍然是全球死亡的主要原因，据信2018年有960万人死于癌症（约占死亡人数的六分之一）。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势必会增加。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来对抗疾病，也可以用来对抗癌症。它使用人体或实验室制造的物质来改善人体免疫系统的工作方式，以发现和摧毁癌细胞。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“武装”它们，使其具有检测和摧毁肿瘤细胞的能力。这些所谓的“嵌合抗原受体（CAR -T）”或“CAR- nk”细胞已经彻底改变了患有其他无法治愈的癌症的患者的治疗方法。然而，到目前为止，这些疗法主要依赖于从患者或健康捐赠者身上收集这些血细胞。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，并且需要复杂的基础设施来交付。另一个问题是在一些使用CAR-T细胞疗法的患者中出现的不良副作用。因此，任何寻求减少可变性、降低成本、提高安全性、使制造过程更快和/或更健壮的疗法都极具吸引力。其中一个研究领域是“诱导多能干细胞”（iPSCs）的使用。这些细胞可以从成人组织中制造出来，并且具有在实验室中无限期培养的能力，更重要的是，它们可以在体内产生任何类型的细胞——这使它们成为制造现成细胞疗法的理想起始材料。它们也非常适合基因改造，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的。第一个是利用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。二是利用Plasticell的下一代筛选技术，开发高效的方法来生成ipsc衍生的自然杀伤细胞。这两种技术的结合有望创造一种负担得起的、有效的、安全的癌症治疗方法。

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.