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. 2008 Sep 26;26(41):5315-20.
doi: 10.1016/j.vaccine.2008.07.036. Epub 2008 Aug 3.

VSports在线直播 - Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors

Duane A Sewell  1 , Zhen Kun Pan, Yvonne Paterson
Affiliations

"V体育2025版" Listeria-based HPV-16 E7 vaccines limit autochthonous tumor growth in a transgenic mouse model for HPV-16 transformed tumors

Duane A Sewell et al. Vaccine. .

VSports app下载 - Abstract

We have shown that Listeria-based cancer vaccines inhibit the growth of transplanted tumors in a transgenic mouse model of immune tolerance where HPV-16 E7 is expressed in the thyroid gland VSports手机版. In this study we determine whether these vaccines are able to inhibit autochthonous tumor growth in this animal model. Mice treated with Listeria vaccines expressing E7 had significantly smaller thyroid tumors than did mice treated with controls and possessed higher numbers of antigen-specific CD8(+) T cells within the spleens, tumors, and peripheral blood. This study shows that Listeria-based vaccines are able to slow autochthonous tumor growth and break immunological tolerance. .

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Figure 1
Figure 1. Reduction in thyroid gland mass after vaccinations with Listeria-based vaccines
After 8 months of vaccinations with Listeria-based vaccines, thyroid glands from transgenic mice were harvested and measured. Individual sizes from each of the four groups are shown. The experiment was performed twice. In both experiments, the difference in average sizes between each of the experimental groups (Lm-ActA-E7 and Lm-LLO-E7) and the negative control groups (naïve and Lm-LLO-NP) is statistically significant (P<0.001, one-way ANOVA).
Figure 2
Figure 2. Tetramer analysis of E7-specific lymphocytes in the spleens of vaccinated transgenic mice
Splenocytes were pooled from 5 mice in each vaccine group one week after 8 months of monthly vaccinations. They were stained with antibodies to CD8, CD62L, and E7/Db tetramer and the data analyzed by flow cytometry. The experiment was performed twice. Shown are representative plots from one experiment. These data show that Lm-LLO-E7 and Lm-ActA-E7 generate increased numbers of E7-specific lymphocytes in the spleens of transgenic animals when compared to controls.
Figure 3
Figure 3. Tetramer analysis of E7-specific TILs from the thyroid glands of transgenic mice
Single cell suspensions from thyroids were pooled from 5 mice in each vaccine group one week after 8 months of monthly vaccinations. They were stained with antibodies to CD8, CD62L, and E7/Db tetramer and the data analyzed by flow cytometry. The experiment was performed twice. Shown are representative plots from one experiment. These data show that Lm-LLO-E7 and Lm-ActA-E7 administration stimulates E7-specific T lymphocytes in the thyroid gland.
Figure 4
Figure 4. Tetramer analysis of E7-specific lymphocytes PBMC from vaccinated transgenic mice
PMBCs from 5 mice in each vaccine group one week after 8 months of monthly vaccinations. They were stained with antibodies to CD8, CD62L, and E7/Db tetramer and the data analyzed by flow cytometry. The experiment was performed twice. Shown are representative plots from one experiment. These data show that Lm-LLO-E7 and Lm-ActA-E7 administration stimulates E7 specific T lymphocytes in the peripheral blood.
Figure 5
Figure 5. ELISPOT assay of PBMCs and TILs from transgenic mice
PBMC (a) and thyroid infiltrating lymphocytes (b) from vaccinated transgenic mice were harvested one week after the eighth and final vaccination with the Listeria constructs, and standard IFN-γ ELISPOT assays were performed. Mice vaccinated with Lm-LLO-E7 and Lm-ActA-E7 demonstrated significantly more spot forming colonies than controls (p<0.0001, one-way ANOVA). SFCs = spot-forming colonies.
Figure 5
Figure 5. ELISPOT assay of PBMCs and TILs from transgenic mice
PBMC (a) and thyroid infiltrating lymphocytes (b) from vaccinated transgenic mice were harvested one week after the eighth and final vaccination with the Listeria constructs, and standard IFN-γ ELISPOT assays were performed. Mice vaccinated with Lm-LLO-E7 and Lm-ActA-E7 demonstrated significantly more spot forming colonies than controls (p<0.0001, one-way ANOVA). SFCs = spot-forming colonies.
Figure 6
Figure 6. E7-specific antibody production in wild-type and transgenic mice after vaccination
Serum samples were harvested one week after the eighth immunization and diluted serially in PBS and standard ELISA assays were performed as described. The y axis represents 100 × Log4 dilutions. In both wild type (a) and transgenic (b) mice, statistically significant increases in E7-specific antibody production were seen in Lm-LLO-E7 and Lm-ActA-E7 vaccinated mice (p<0.0001, one way ANOVA). W=wild type mice, T=transgenic: N=naïve; G=Lm-LLO-E7; A= Lm=ActA-E7; NP=Lm-LLO-NP
Figure 6
Figure 6. E7-specific antibody production in wild-type and transgenic mice after vaccination
Serum samples were harvested one week after the eighth immunization and diluted serially in PBS and standard ELISA assays were performed as described. The y axis represents 100 × Log4 dilutions. In both wild type (a) and transgenic (b) mice, statistically significant increases in E7-specific antibody production were seen in Lm-LLO-E7 and Lm-ActA-E7 vaccinated mice (p<0.0001, one way ANOVA). W=wild type mice, T=transgenic: N=naïve; G=Lm-LLO-E7; A= Lm=ActA-E7; NP=Lm-LLO-NP
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