Nanotechnology to Genetically Reprogram Tumor Cells for Treatment of Metastatic Ovarian Cancer
Abstract
Ovarian cancer is the second most common gynecological cancer and has the lowest survival rate. Immunotherapy holds promise for the treatment of ovarian cancer, in which high numbers of cytotoxic T cells correlate with better prognosis. Antigen presenting cells (APCs) normally activate T cells by coordinated presentation of SIGNAL 1 (tumor antigen in the context of major histocompatibility complex class I, MHC I), SIGNAL 2 (surface-bound co-stimulatory molecule; here, 4-1BBL), and SIGNAL 3(secreted cytokines; here, IL-12). We are working on using nanoparticles (NPs) based on biodegradable poly(beta-aminoester)s (PBAEs) to deliver key genetic factors to ovarian cancer cells in vivo to reprogram them into immunostimulatory cells, mimicking the expression patterns of APCs to promote productive antigen presentation to T cells. This is accomplished by transfecting signal 1-expressing cells with signals 2 and 3, leading to T-cell activation in an antigen-restricted manner. During the first reporting period, we focused on optimizing NP-mediated transfection of tumor cells in vitro and in vivo which will allow us to genetically engineer them with immunostimulatory genes in the next reporting period.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2022
- Accession Number
- AD1184649
Entities
People
- Jordan J Green
Organizations
- Johns Hopkins University