Despite progress in conventional therapies, including surgery, radiotherapy, and chemotherapy, as well as the development of new immunotherapies like immune checkpoint blocking antibodies (ICB), survival outcomes of patients with glioblastoma (GBM) have not significantly improved. Previous research has demonstrated both GBM patients and murine models of GBM exhibit systemic immunosuppression, but the nature of this immune deviation is poorly understood, and its impact on anti-tumor immune therapy remains unclear. My long-term research goal is to use an interdisciplinary approach that fuses materials engineering and immunology to identify the key factors that overcome the immunosuppression an...

Read More

Despite progress in conventional therapies, including surgery, radiotherapy, and chemotherapy, as well as the development of new immunotherapies like immune checkpoint blocking antibodies (ICB), survival outcomes of patients with glioblastoma (GBM) have not significantly improved. Previous research has demonstrated both GBM patients and murine models of GBM exhibit systemic immunosuppression, but the nature of this immune deviation is poorly understood, and its impact on anti-tumor immune therapy remains unclear. My long-term research goal is to use an interdisciplinary approach that fuses materials engineering and immunology to identify the key factors that overcome the immunosuppression and drive the effective anti-tumor immune responses in GBM, develop new therapeutic strategies to enhance cancer immunotherapy, and ultimately translate these findings and strategies into clinical applications for the treatment of human brain cancer patients in Texas. My objective in this application is to leverage my expertise in polymer synthesis, nanoparticle fabrication, biomedical engineering, and immunology to achieve three specific aims. First, I will use a toll-like receptor nanoparticle therapeutic that I developed, which has demonstrated potent therapeutic efficacy in a murine orthotopic GBM model, to investigate the mechanisms by which this nanoparticle drives effective anti-tumor immune responses against GBM. Second, I will design and synthesize a series of new nanoparticles with fine-tuned properties and determine the optimal materials criteria for enhancing immune activation and inducing robust and durable anti-GBM immune responses. Third, I will use both orthotopic murine tumor models and human cancer patient-derived tumor organoids to translate these optimized therapeutics into clinical applications.

Read Less