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

Abstract Metastatic cancer, particularly metastatic melanoma, poses a significant therapeutic challenge due to its resistance to standard treatments and low five-year survival rate of 20–27%. Current therapies show limited success, highlighting the urgent need for novel interventions. 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 for mice treated with DoriVac in both the B16OVA and B16F10 melanoma mouse models. DoriVac also appears to be a safe and effective treatment, with no anti-drug antibodies, as indicated by lower anti-dsDNA levels. Importantly, we observed an amplified effect when DoriVac was combined with 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. These findings suggest that DoriVac, particularly in combination with the αPD-L1 immune checkpoint blockade, can serve as a promising immunotherapy against metastatic cancer.