Unmet Need
Melanoma is an aggressive form of skin cancer that is characterized by high multidrug resistance and low survival rates. The median survival time for metastatic melanoma patients is approximately 8-9 months with a 3-year overall survival rate of less than 15%. As such, there is a compelling need for novel targeted melanoma therapies.
Immunotherapy has shown clinical success in treating cancers that are unresponsive to chemotherapeutic treatments. This requires immune cells to be activated to recognize tumor antigens, after which they can seek out and destroy cancer cells. For T-cell immunotherapy, antigen-presenting cells (APCs) normally activate CD8+ cytotoxic T-cells by presenting a ‘signal 1’, consisting of a major histocompatibility complex (MHC) I molecule with an antigen peptide, a co-stimulatory ‘signal 2’ that directs the action of the T-cells upon recognition of the tumor antigen, and a secreted ‘signal 3’ for recruitment and differentiation of immune cells.
Technology Overview
Researchers at Johns Hopkins University have recently developed a synthetic poly(beta-amino ester) (PBAE)-based nanoparticle gene delivery system. This invention uses synthetic nanoparticles to transfect melanoma cells with two DNA-encoding gene molecules, ‘signals 2 and 3’, respectively; one co-stimulatory protein (e.g., 4-1BBL, CD80, CD86, OX40L) and a secreted cytokine protein (e.g., IL-2, IL-12, IL-15) effectively reprogramming these cells into tumor-derived APCs (tAPCs). By delivering two specific types of exogenous immune stimulatory signals to tumor cells already expressing intrinsic tumor antigens (‘signal 1’), this novel immunotherapy creates a functional ‘antigen-agnostic’ tAPC capable of eliciting the bodies T-cell response and has the potential to be broadly applicable to multiple types of hard to-treat tumors such as melanoma.
Stage of Development
In vivo mouse model and in vitro data available
Publications
Wilson D et al. ‘Non-Viral Genetic Reprogramming of Tumor Cells for Self-Directed Cancer Immunotherapy’, 2018 Biomedical Engineering Society Annual Meeting, Oct. 17-20, Atlanta, Georgia.
Tzeng SY et al. In situ genetic engineering of tumors for long-lasting and systemic immunotherapy. PNAS 117 (8) 4043-4052.
