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

这个小型企业创新研究(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天然的抗癌防御系统，即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，并可以针对实体瘤和血癌。这使得NK细胞在治疗许多类型的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，方法是修改NK细胞，使其对体内的癌细胞更具反应性。这些改良的NK细胞有可能与目前的治疗方法相结合，在不增加患者副作用的情况下提高其有效性。该项目有可能使数百万人受益，特别是在美国，据估计，40%的人将在一生中的某个时候被诊断出患有癌症。该项目将使用一种获得专利的表观遗传修饰物来增强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，改变遗传密码也有相关的风险，通常细胞疗法可能只对非常特定的癌症亚型有效。表观遗传修饰物不会改变潜在的DNA序列，但可以有效地改变基因表达。此外，NK细胞可以针对广泛的癌症，但在许多癌症患者中，它们的肿瘤杀伤能力往往受到抑制。研究目标是使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，使其对检测和杀死癌细胞更加敏感。在锁定关键基因后，将评估NK细胞增强的肿瘤杀伤能力以及这种能力持续多长时间。更具体地说，这个项目试图证明，从健康捐赠者身上提取的NK细胞可以进行表观遗传改变，以增强其自然杀伤肿瘤细胞的功能。这一解决方案将为开发NK细胞疗法奠定基础，从健康捐赠者中分离出来的NK细胞经过表观遗传修饰以增强其活性，然后交付给癌症患者用于寻找和杀死他们的癌细胞。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.