SBIR Phase I: A non-viral gene editing platform for cell therapies in the veterinary market

这个小型企业创新研究(SBIR)第一阶段项目的更广泛影响是推进了一种治疗癌症的新方法。拟议的项目将使用重新编程的活免疫细胞来识别和摧毁癌症。这里开发的技术可以用于治疗狗的这种疾病，并最终用于人类。拟议的项目重点是将新的基因编辑技术应用于细胞疗法的工程，并展示所产生的治疗方式在犬身上的安全性。这种治疗方法是用嵌合抗原受体重新编程的人类T免疫细胞，嵌合抗原受体被改造成与CD20(chCAR20-T细胞)结合，CD20是一种发现在癌细胞B细胞表面的蛋白质。确定最佳的基因传递和基因编辑条件是在不使用病毒的情况下增强CAR-T细胞制造的主要重点。这些优化的方法将被用于产生剂量的同种异体chCAR20-T细胞，并针对多个CD20+犬癌株进行测试，以确认它们的细胞毒活性。这项提议的最终目标是将chCAR20-T细胞移植到实验室犬体内，以证明在体内是安全的。这一制造平台可以应用于人类细胞疗法的开发。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 of this Small Business Innovation Research (SBIR) Phase I project is to advance a novel way to treat cancer. The proposed project will use of reprogrammed, living immune cells to recognize and destroy cancer. The technology developed here can be used for treatment of this disease in dogs, and ultimately for humans. The proposed project is focused on application of novel gene editing technology to the engineering of cell therapies and demonstrating the safety of the resultant therapeutic modality in canines. This therapeutic modality is a human T immune cell reprogrammed with a Chimeric Antigen Receptor engineered to bind to CD20 (chCAR20-T cells), a protein found on the surface of cancerous B cells. Identifying optimal gene delivery and gene editing conditions is a primary focus towards enhanced manufacturing of CAR-T cells without the use of a virus. These optimal methods will be used to generate doses of allogeneic chCAR20-T cells and tested against multiple lines of CD20+ canine cancers in order to confirm their cytotoxic activity. The final objective of this proposal is to transplant chCAR20-T cells into laboratory canines to prove safety in vivo. This manufacturing platform can be applied to the development of human cell therapies.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.