Designer Nanoparticles for Immunotherapeutic Treatment of Bladder Cancer
Abstract
Bladder cancer is a common cancer with more than 70,000 new cases and 15,000 deaths annually in the United States. Bladder cancer is the 4th most common cancer in veterans at 3.6%, behind only prostate, lung and colon cancer. For metastatic, advanced stage bladder cancer, 5 immune checkpoint inhibitors have been approved in the last several years. These drugs have revolutionized the treatment of metastatic bladder cancer, providing durable, and well tolerated responses in ~20% of patients. However, the treatment of localized disease remains unchanged and immune checkpoint inhibitors have not been integrated into the care of these patients. Objective/hypothesis: In this application, we propose to develop a designer nanoparticle based on bacteriophage lambda where we have coopted the non-infectious capsid which can be decorated with targeting antibodies, bioactive proteins, DNA, fluorophores, etc., in defined ratios. Specifically, we propose to develop theranostic phage-like particles or PLPs which are decorated with fluorescein, anti-epidermal growth factor receptor (EGFR) and/or CD47 targeting capabilities, and interferon stimulatory DNAs (ISDs) that activate the stimulator of interferon genes (STING) pathway to promote an anti-tumor immune response. We hypothesize that PLPs can be optimized to activate the STING pathway resulting in production of Type I interferons (IFN alpha and beta) leading to a robust and durable anti-tumor immune response. We have generated preliminary data demonstrating engineering of the PLPs and specific uptake into bladder cancer cells. Impact: There is a substantial clinical gap in the treatment of early-stage bladder.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1193638
Entities
People
- Jared Brown
Organizations
- University of Colorado Boulder