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

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.