SBIR Phase I: Epigenetic Remodeling of Natural Killer (NK) Cells for Blood Cancer Therapies

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是产生更好的癌症治疗替代方案。新的解决方案将利用人体的天然抗癌防御系统，一种被称为自然杀伤细胞或NK细胞的免疫细胞。NK细胞能够识别体内几乎所有的癌细胞，可以针对实体瘤和血癌。这使得NK细胞在治疗多种癌症方面具有广泛的吸引力。该团队提出了一种广谱癌症治疗方法，通过修改NK细胞，使其对体内的癌细胞更有反应。这些经过修饰的NK细胞可能会与目前的治疗方法相结合，以提高其有效性，而不会增加患者的副作用。这个项目有可能使数百万人受益，特别是在美国，据估计，40%的人将在他们生命的某个阶段被诊断出患有癌症。该项目将使用一种获得专利的表观遗传修饰剂来增强NK细胞的肿瘤杀伤能力。许多基于免疫细胞的疗法依赖于改变用于治疗疾病的细胞的遗传密码。然而，改变遗传密码有相关的风险，而且细胞疗法通常只对一种非常特定的癌症亚型有效。表观遗传修饰不改变潜在的DNA序列，但可以有效地改变基因表达。此外，NK细胞可以靶向广谱的癌症，但在许多癌症患者中，它们的肿瘤杀伤能力往往受到抑制。研究目标是利用获得专利的表观遗传修饰物来增加NK细胞关键基因的表达，使其更敏感地检测和杀死癌细胞。在靶向关键基因后，将评估NK细胞是否增加了肿瘤杀伤能力，以及这种能力持续多久。更具体地说，该项目旨在证明从健康供体中提取的NK细胞可以通过表观遗传改变来增强其杀死肿瘤细胞的自然功能。该解决方案将为开发NK细胞疗法奠定基础，从健康供体中分离的NK细胞经过表观遗传修饰以增强其活性，然后将其传递给癌症患者以猎杀并杀死其癌细胞。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to produce better alternatives to cancer treatment. The new solution will take advantage of the body’s natural anticancer defense system, an immune cell called a natural killer cell or NK cell. NK cells are able to recognize almost any cancerous cell in the body and can target both solid tumors and blood cancers. This gives NK cells a broad appeal for the treatment of many types of cancer. The team proposes a broad-spectrum cancer treatment by modifying NK cells to be more reactive to cancerous cells in the body. These modified NK cells could potentially be combined with current therapies to enhance their effectiveness, without increasing side-effects in patients. This project has the potential to benefit millions of people, especially in the United States where it is estimated that 40% of individuals will be diagnosed with cancer at some point in their life. This project will use a patented epigenetic modifier to enhance the tumor killing abilities of NK cells. Many immune cell-based therapies rely on altering the genetic code of the cell that will be used to treat disease. However, there are associated risks in altering the genetic code and often the cell therapy may only work on a very specific subtype of cancer. Epigenetic modifiers do not change the underlying DNA sequence but can effectively alter gene expression. Furthermore, NK cells can target a broad-spectrum of cancers but in many cancer patients their tumor killing ability is often suppressed. The research goal is to use the patented epigenetic modifier to increase expression of key NK cells genes that will make them more sensitive to detecting and killing cancer cells. After targeting key genes, NK cells will be assessed for increased tumor killing ability and for how long this ability persists. More specifically, this project seeks to demonstrate that NK cells taken from a healthy donor can be epigenetically altered to enhance their natural function of killing tumor cells. This solution will lay the groundwork to develop a NK cell therapy where NK cells isolated from healthy donors are epigenetically modified to enhance their activity, then delivered to cancer patients to hunt and kill their cancer cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.