Engineering Natural Killer Cells to Increase their Potency

改造自然杀伤细胞以提高其效力

• 批准号: 560412-2020
• 负责人: Haddad, Elie
• 金额: $ 4.42万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=707089
• 关键词: Engineering; Natural; Killer; Cells; Increase

The immune system has evolved to specifically recognize, target and kill infection and malignant cells. However, in several severe diseases, its capacity is dampened by the infectious agent or the tumor environment, limiting its scope of efficacy. For example, the severity of COVID-19 disease has been associated with a decreased number of immune cytotoxic cells, and these cells were found to be exhausted, meaning that they could no longer do their role in an effective way. In this proposal, we propose to apply state-of-the-art gene and cell engineering to the immune system to create tools that could be used to control viral infections or cancer. Natural Killer (NK) cells, which are white blood cells specialized in detection and elimination of viral infected cells and malignant cells, are interesting cell candidate to harness as they are safe and they can be administered regardless the compatibility of the donor. Hence, it would be interesting to modify them to enhance their potency. However, NK cells are notoriously difficult to engineer. To circumvent this issue, we have built a team of academic researchers in cell engineering and a Canadian biotechnology company, Feldan Therapeutics. Our team develops techniques to engineer NK cells to be more resistant to exhaustion (Feldan Therapeutic's technology) and to make them recognize more efficiently malignant cells or cells infected by virus, such as the SARS-CoV-2 (Dr. Haddad's laboratory's technology). In this project, we will devise innovative ways to create a new generation of engineered NK cells with increased potency and we will test the impact of these modifications on their function, survival and safety. If proven effective, this technology would be versatile and could significantly impact Feldan's business strategy by positioning the company as a leader in cell-based immuno-oncology by providing a breakthrough technology based on their Shuttle technology.

免疫系统已经进化到能够特异性识别、瞄准和杀死感染细胞和恶性细胞。然而，在一些严重疾病中，其能力会受到传染源或肿瘤环境的削弱，从而限制了其疗效范围。例如，COVID-19疾病的严重程度与免疫细胞毒性细胞数量的减少有关，并且这些细胞被发现已经耗尽，这意味着它们无法再以有效的方式发挥作用。在这项提案中，我们建议将最先进的基因和细胞工程应用于免疫系统，以创建可用于控制病毒感染或癌症的工具。自然杀伤 (NK) 细胞是一种白细胞，专门用于检测和消除病毒感染细胞和恶性细胞，是值得利用的候选细胞，因为它们很安全，并且无论捐赠者的兼容性如何都可以进行施用。因此，修改它们以增强它们的效力将是很有趣的。然而，众所周知，NK 细胞很难改造。为了解决这个问题，我们建立了一个由细胞工程领域的学术研究人员和加拿大生物技术公司 Feldan Therapeutics 组成的团队。我们的团队开发了一些技术，使 NK 细胞更能抵抗衰竭（Feldan Therapeutic 的技术），并使其更有效地识别恶性细胞或病毒感染的细胞，例如 SARS-CoV-2（Haddad 博士实验室的技术）。在这个项目中，我们将设计创新方法来创建具有更高效力的新一代工程 NK 细胞，并且我们将测试这些修饰对其功能、存活和安全性的影响。如果被证明有效，这项技术将具有多种用途，并可通过提供基于其 Shuttle 技术的突破性技术，将公司定位为基于细胞的免疫肿瘤学领域的领导者，从而对 Feldan 的业务战略产生重大影响。