STTR Phase I: Metabolite-based Polymer-loaded Chimeric Antigen Receptor Expressing Metabolically-Fit Immune Cells for Immunotherapy

这项小企业技术转让（STTR）第一阶段项目的更广泛影响是改善癌症治疗。这个项目提出了一种新的治疗方法，针对癌细胞和解决他们的恶性肿瘤。在淋巴瘤的初步应用之后，本文获得的结果可以应用于几种类型的癌症。拟议中的项目将产生基于嵌合抗原受体（CAR）的细胞疗法，以改善淋巴瘤的治疗。目前，这些疗法在到达肿瘤微环境后出现了细胞因子释放综合征和代谢衰竭等负面影响。此外，肿瘤微环境中CAR细胞的低营养利用率降低了疗效。因此，利用CAR疗法帮助靶向肿瘤并保持这些细胞充分代谢以发挥其功能的策略是有益的。该项目的主要目标是测试在资源贫乏的环境中产生维持免疫细胞激活的生物材料的可行性。该项目将生成car -巨噬细胞，并测试我们的生物材料在这些细胞中维持代谢适应性的能力。技术活动包括：(1)使用非病毒电穿孔产生人类CAR巨噬细胞，(2)证明人类CAR巨噬细胞可以在资源匮乏的环境中存活，以及(3)证明小鼠CAR巨噬细胞在小鼠体内不会诱导毒性。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 of this Small Business Technology Transfer (STTR) Phase I project is to improve cancer treatment. This project advances a new therapy that targets cancer cells and addresses their malignancies. Following the initial application of lymphomas, the results obtained herein can be applied to several types of cancer.The proposed project will generate Chimeric Antigen Receptor (CAR)-based cell therapies to improve treatment for lymphomas. Currently, these therapies show negative effects, such as cytokine release syndrome and metabolic exhaustion upon reaching the tumor microenvironment. Furthermore, low nutrient availability for CAR cells in the tumor microenvironment decreases the efficacy. Therefore, strategies utilizing CAR therapy to help target the tumors and keep these cells sufficiently metabolically fit to perform their functions are beneficial. The main goal of this project is to test the feasibility of generating biomaterials that maintain activation of immune cells in resource-poor environments. This project will generate CAR-macrophages and test the ability of our biomaterials to maintain metabolic fitness in these cells. Technical activities include: (1) Generate human CAR macrophages using non-viral electroporation, (2) Show proof-of-concept that human CAR macrophages can survive in a resource-poor environment, and (3) Show proof-of-concept that mouse CAR macrophages do not induce toxicity in vivo in mice.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.