DNA-based nanotechnology stimulates potent antitumor immune responses
Synthetic DNA nanovaccines enhance killer T cell immunity resulting in tumor control in preclinical studies
- Date:
- September 10, 2020
- Source:
- The Wistar Institute
- Summary:
- Combining their expertise in protein engineering and synthetic DNA technology, scientists successfully delivered nanoparticle antitumor vaccines that stimulated robust CD8 T cell immunity and controlled melanoma growth in preclinical models.
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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," said Ziyang Xu, Ph.D., a recent doctoral graduate working at Wistar and the first author of the study. "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."
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.
Story Source:
Materials provided by The Wistar Institute. Note: Content may be edited for style and length.
Journal Reference:
- Ziyang Xu, Neethu Chokkalingam, Edgar Tello-Ruiz, Megan C Wise, Mamadou A Bah, Susanne Walker, Nicholas J Tursi, Paul D Fisher, Katherine Schultheis, Kate E Broderick, Laurent Humeau, Daniel W Kulp and David B Weiner. A DNA-launched nanoparticle vaccine elicits CD8 T-cell immunity to promote in vivo tumor control. Cancer Immunology Research, 2020 DOI: 10.1158/2326-6066.CIR-20-0061
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