Researchers designed DLnano-vaccines displaying 60 copies of protein parts derived from the melanoma-specific antigens Trp2 and Gp100 and tested these in mouse models of melanoma, observing prolonged survival that depended on CD8 T cell activation both in therapeutic and prophylactic settings.
One of the advantages of synthetic DNA technologies over other methods is the versatility of the platforms. DLnano-vaccines may be designed for various cancer targets and our study shows this is a promising strategy for cancer immunotherapy that may warrant further testing."
Ziyang Xu, Ph.D., a recent doctoral graduate working at Wistar and first author of the study
To elucidate the mechanism through which DLnano-vaccines activate CD8 T cells, the team studied the effects of the DNA-launched version of a previously described HIV nanoparticle vaccine (eOD-GT8-60mer). They observed that DLnano-vaccines administered via electroporation resulted in transient muscle cell apoptosis that attracted macrophage infiltration at the injection site, which in turn was instrumental to activate CD8 T cells.
DLnano-vaccines were developed using synthetic DNA technology in collaboration with the lab of David B. Weiner, Ph.D., Wistar executive vice president, director of the Vaccine & Immunotherapy Center, and the W.W. Smith Charitable Trust Professor in Cancer Research and also a co-senior author on the study.
Xu, Z., et al. (2020) A DNA-launched nanoparticle vaccine elicits CD8+ T-cell immunity to promote in vivo tumor control, Cancer Immunology Research. doi.org/10.1158/2326-6066.CIR-20-0061.