There was a clear correlation between percentage of GFP DC 1 cells and amount of L1 protein in HPV 16GFP psV, as demonstrated selleck catalog by the increase in GFP expression in DC 1 cells with increasing amount of L1 protein in HPV 16GFP psV. As shown in Figure 2B, DC 1 cells infected with HPV 16GFP psV Inhibitors,Modulators,Libraries showed a clear shift in the peak of GFP expres sion compared to that of uninfected cells, indicating that the Inhibitors,Modulators,Libraries majority of cells infected with HPV 16GFP psVs had significantly greater GFP expression than uninfected cells. Thus, our data suggest that HPV pseu dovirions can efficiently infect dendritic cells in vitro in a dose dependent manner. Treatment of tumor bearing mice with DNA delivered by HPV 16 pseudovirions generates therapeutic antitumor effects We have previously demonstrated that C57BL6 mice vaccinated with HPV 16 pseudovirions carrying OVA DNA were capable of preventing tumor growth upon challenge with OVA expressing tumor.
To determine if DNA Inhibitors,Modulators,Libraries delivered by HPV 16 pseudovirions could gener ate appreciable therapeutic antitumor effects, we per formed in vivo tumor treatment experiments. C57BL6 mice were inoculated subcutaneously with B16OVA tumor cells and treated with the various Inhibitors,Modulators,Libraries vaccination groups three days later. Mice were boosted with the same regimen on day 10 and 17 after tumor inoculation. As shown in Figure 3, tumor bearing mice treated with HPV 16OVA psV demonstrated significantly reduced tumor volume as compared to tumor bearing mice trea ted with HPV 16 pseudovirions carrying DNA encoding irrelevant protein or untreated mice.
Thus, our data suggest Inhibitors,Modulators,Libraries that treatment with HPV 16 pseudovirions carrying OVA DNA can generate therapeutic antitumor effects against OVA expressing tumors in tumor bearing mice. Vaccination with DNA delivered by HPV 16 pseudovirions generates the highest levels of antigen specific CD8 T cell immune responses compared to vaccination with DNA delivered by other methods We next compared the OVA specific CD8 T cell immune responses generated by vaccination with OVA specific DNA vaccines delivered by different methods including intramuscular injection followed by electro poration, gene gun, and HPV 16 pseudovirions. As shown in Figure 4, C57BL6 mice vaccinated subcuta neously with HPV 16OVA psV generated the highest number of OVA MHC class I peptide speci fic CD8 T cell immune responses among all vaccina tion groups.
In addition, we observed that DNA vaccine delivered by intramuscular injection followed by electro poration and DNA vaccine delivered by gene gun both generated higher OVA specific CD8 T cell immune responses at a higher dose of DNA compared to a lower dose of DNA. Furthermore, we observed that delivery sellectchem of DNA vaccine by HPV 16 pseudovirions generated a significantly higher antigen specific CD8 T cell immune response even with a lower dose of DNA vaccine contained in the pseudovirion.