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

STTR 第一阶段：基于代谢物的聚合物负载嵌合抗原受体，表达代谢适合的免疫细胞，用于免疫治疗

• 批准号: 2151586
• 负责人: Mamta Wankhede
• 金额: $ 25.6万
• 依托单位: AXILEA LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2151586&HistoricalAwards=false
• 关键词: STTR; Phase; Metabolite; based; Polymer

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.

这个小企业技术转让（STTR）第一阶段项目的更广泛影响是改善癌症治疗。该项目提出了一种新的治疗方法，靶向癌细胞并解决其恶性肿瘤。 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，这些疗法显示出负面影响，如细胞因子释放综合征和到达肿瘤微环境后的代谢衰竭。此外，肿瘤微环境中CAR细胞的低营养可用性降低了疗效。因此，利用CAR疗法来帮助靶向肿瘤并保持这些细胞在代谢上足够适合执行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。该项目将产生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CAR巨噬细胞，（2）显示人CAR巨噬细胞可以在资源贫乏的环境中存活的概念验证，（3）证明-该奖项反映了NSF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进行评估，被认为值得支持的搜索.