Engineering Natural Killer Cells to Increase their Potency

免疫系统已经进化到能够识别、瞄准并杀死感染细胞和恶性细胞。然而，在一些严重的疾病中，它的能力受到感染因子或肿瘤环境的抑制，限制了它的作用范围。例如，COVID-19疾病的严重程度与免疫细胞毒性细胞数量减少有关，这些细胞被发现已经耗尽，这意味着它们不能再以有效的方式发挥作用。在这个建议中，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。自然杀伤细胞（NK）是一种专门检测和消除病毒感染细胞和恶性细胞的白细胞，是一种有趣的候选细胞，因为它们是安全的，可以不考虑供体的相容性而给予。因此，修改它们以增强它们的效力将是有趣的。然而，NK细胞是出了名的难以改造的。为了解决这个问题，我们在细胞工程和加拿大生物技术公司Feldan Therapeutics建立了一个学术研究团队。我们的团队开发技术，使NK细胞更能抵抗衰竭（Feldan therapeutics的技术），并使它们更有效地识别恶性细胞或被病毒感染的细胞，如SARS-CoV-2（哈达德博士的实验室技术）。在这个项目中，我们将设计创新的方法来创造具有更高效力的新一代工程NK细胞，我们将测试这些修饰对其功能，生存和安全性的影响。如果这项技术被证明是有效的，它将是通用的，并可能显著影响Feldan的商业战略，通过提供基于他们的Shuttle技术的突破性技术，使公司成为基于细胞的免疫肿瘤学的领导者。

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.