Design Considerations for Potent DNA-Platform-Based Cancer Vaccines

Cancer vaccines have the potential to harness the strength of our immune system to fight cancer safely and effectively, but their potency relies on the presentation and tuned delivery of the vaccine's components. Different than other delivery platforms, DNA-based nanostructures are highly programmable architectures that allow for precise control of size, geometry, flexibility, and spatial organization of the scaffold and conjugated moieties. The modularity of DNA-based nanostructures enables the field to consider and program various determinants of vaccine potency including biodistribution, cargo protection, cellular uptake, and intracellular processing. Consequently, numerous design strategies have emerged using various DNA-based materials. Collectively, these developments have illustrated how slight alterations in structure notably impacts the directions and strengths of the resulting immunostimulatory responses against tumors. As the relationship between structure and immunomodulation becomes increasingly understood, the potential of DNA-based nanostructures to serve as precise and potent cancer vaccine delivery platforms will be further realized.