Project 458266

Traditional therapeutic cancer vaccine approaches typically involve injecting cancer patients with antigens (molecules that can trigger an immune response) specific to their own tumors, along with immune-stimulating agents called adjuvants, to amplify the response. However, the clinical success of traditional cancer vaccines has been limited by 1) the complexity of identifying patient-specific antigens and 2) the inefficient delivery of these antigens to the antigen presenting cells (APCs) of the immune system. Alternatively, broad immune-stimulating adjuvants can be directly injected into tumors to trigger APCs in the tumor into killing tumor cells, an approach termed in-situ vaccination. Unfortunately, adjuvants can be taken up by cells non-specifically causing dose-limiting toxicity and can induce inflammatory toxicity when administered systemically. Therefore, efficient delivery of adjuvants to APCs in the tumour is imperative for successful vaccination. Nanostructures are a promising class of carriers for delivering adjuvants to APCs because 1) APCs preferentially take up nanoscale materials, and 2) the surface of the nanostructures can be outfitted with high affinity ligands for APC cell-surface receptors. However, how the specific nanoscale design features, such as nanostructure shape and ligand spatial arrangement, can combine to promote nanostructure uptake by APCs remains unclear. A major limitation has been the inability to precisely control these design parameters in existing nanomaterials. Using emerging advances in the field of DNA nanotechnology, I will investigate how nanostructure design can optimize adjuvant delivery to APCs ultimately leading to tumour eradication. The results of this research will provide a much needed outlook on how nanotechnology design can be leveraged in an in-situ cancer vaccine approach to provide a tangible clinical impact for cancer patients.