Validation of DoriVac (DNA Origami Vaccine) Efficacy in a Metastatic Melanoma Model

Metastatic cancer, particularly metastatic melanoma, poses a significant therapeutic challenge due to its resistance to standard treatments and a low five-year survival rate of 20-27%. Recent advances in cancer vaccine research show great promise in reducing disease recurrence, but these approaches still face challenges pertaining to antigen selection, ease of production, and programmability. To address some of these challenges, we have adapted the DoriVac platform to serve as a cancer vaccine against metastatic melanoma. DoriVac is a DNA origami-based vaccine platform that allows for the codelivery of antigens of choice and the CpG immune adjuvant at an optimal nanospacing to promote Th1 immune polarization. In our study, we observed a significant reduction in lung tumor nodules in the B16OVA and B16F10 melanoma models for DoriVac-treated mice. DoriVac also appears to be a safe treatment, as we did not observe any significant increase in antinanoparticle (i.e., anti-dsDNA) antibodies. Importantly, we observed an enhanced effect when DoriVac was combined with an αPD-L1 immune checkpoint blockade, leading to an even greater reduction in metastatic lung tumor nodules. Our results also indicate an increased activation of antigen-presenting cells, NK cells, CD4⁺ T cells, and CD8⁺ T cells in comparison to the control groups. These findings suggest that DoriVac, particularly in combination with the αPD-L1 immune checkpoint blockade, can serve as a promising immunotherapy against metastatic cancer.