Biomaterial-Enhanced CAR-T/NK Cell Therapies for Glioblastoma.

This comprehensive research program is focused on revolutionizing the treatment of Glioblastoma (GBM), a highly aggressive brain tumor that currently has limited and largely ineffective treatment options. GBM is known for its devastating impact on patients, often leading to poor prognosis and survival rates. The proposal brings together a multidisciplinary team of experts from various fields, all working towards a common goal - to significantly enhance the efficacy of Chimeric Antigen Receptor (CAR) T-cell therapy using innovative translational biomaterials. The team is driven by a central hypothesis that the strategic use of biomaterial strategies can substantially enhance the effectiveness of CAR therapy. This enhancement is expected to promote epitope spreading, a process that currently limits CAR therapy. The proposal is structured into three distinct but interconnected research projects (RPs), each addressing a unique aspect of the overall goal. The first project (RP1) focuses on the integration of CAR T cell and CAR Natural Killer T (NKT) cell therapy with a specially designed nanofibrous acetalated dextran (Ace-DEX) scaffold that has uniquely tunable release rates. The second project (RP2) is centered on optimizing a Multifunctional Alginate Scaffold for T Cell Engineering and Release (MASTER) system for in situ generation of CAR cells. The third project (RP3) is dedicated to the development of CAR NKT cells, a promising new avenue in immunotherapy. In addition to these research projects, the proposal also includes three cores and three advisory boards. The cores are designed to provide essential support for research projects and include: Core 1: Administrative (Admin) Core; Core 2: Bioinformatics & Immunology; Core 3: Animal Models. They aim to integrate the goals across all projects, identify significant changes in cells of the immune system during GBM development and treatment, and develop pre-clinical mouse models for rigorous testing of these therapies. Our program will be overseen by three advisory boards: The Internal Advisory Board, the Clinical Advisory Board, and the External Advisory Board. The ultimate goal of this proposal is to address the significant challenges in treating GBM and transform the efficacy of CAR T/NKT cell therapies with biomaterials. By achieving this goal, the team hopes to significantly improve the prognosis for GBM patients and contribute to the ongoing efforts to find a cure for this devastating disease. The significance of this proposal lies not only in its potential impact on GBM treatment but also in its potential to advance the field of immunotherapy as a whole. Project Number: 1P01CA298971-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Kristy Ainslie | Institution: UNIV OF NORTH CAROLINA CHAPEL HILL, CHAPEL HILL, NC | Award Amount: $2,554,662 | Activity Code: P01 | Study Section: Special Emphasis Panel[ZRG1 BTC-X (40)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11263854