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Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice

Sofie Denies (UGent) , Bregje Leyman (UGent) , Hanne Huysmans (UGent) , Francis Combes (UGent) , Séan Mc Cafferty (UGent) , Laetitia Cicchelero (UGent) , Marjan Steppe (UGent) , Joyca De Temmerman (UGent) and Niek Sanders (UGent)
(2017) CANCER IMMUNOLOGY IMMUNOTHERAPY. 66(12). p.1545-1555
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Abstract
In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor. The tumor growth, survival, and development of an immune response were followed. The cellular immune response was measured by a bioluminescence-based cytotoxicity assay with vascular endothelial growth factor-2 (VEGFR-2)-expressing target cells. Humoral immune responses were quantified by enzyme-linked immunosorbent assay (ELISA). Ex vivo bioluminescence imaging and immunohistological observation of organs were used to detect (micro)metastases. A cellular and humoral immune response was present in prophylactically and therapeutically vaccinated mice, in both tumor models. Nevertheless, survival in prophylactically vaccinated mice was only moderately increased, and no beneficial effect on survival in therapeutically vaccinated mice could be demonstrated. An influx of CD3+ cells and a slight decrease in VEGFR-2 were noticed in the tumors of vaccinated mice. Unexpectedly, the vaccine caused an increased quantity of early micrometastases in the liver. Lung metastases were not increased by the vaccine. These early liver micrometastases did however not grow into macroscopic metastases in either control or vaccinated mice when allowed to develop further after surgical removal of the primary tumor.
Keywords
Breast cancer, DNA vaccination, Melanoma, Metastasis, VEGFR-2, THERAPEUTIC CANCER VACCINES, DNA VACCINE, GENE-THERAPY, MOUSE MODEL, ANTITUMOR IMMUNITY, DISTANT METASTASIS, ANTI-ANGIOGENESIS, COLORECTAL-CANCER, FACTOR RECEPTOR-2, CELL

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Citation

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MLA
Denies, Sofie, Bregje Leyman, Hanne Huysmans, et al. “Evaluation of a Xenogeneic Vascular Endothelial Growth Factor-2 Vaccine in Two Preclinical Metastatic Tumor Models in Mice.” CANCER IMMUNOLOGY IMMUNOTHERAPY 66.12 (2017): 1545–1555. Print.
APA
Denies, Sofie, Leyman, B., Huysmans, H., Combes, F., Mc Cafferty, S., Cicchelero E, L., Steppe, M., et al. (2017). Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice. CANCER IMMUNOLOGY IMMUNOTHERAPY, 66(12), 1545–1555.
Chicago author-date
Denies, Sofie, Bregje Leyman, Hanne Huysmans, Francis Combes, Séan Mc Cafferty, Laetitia Cicchelero E, Marjan Steppe, Joyca De Temmerman, and Niek Sanders. 2017. “Evaluation of a Xenogeneic Vascular Endothelial Growth Factor-2 Vaccine in Two Preclinical Metastatic Tumor Models in Mice.” Cancer Immunology Immunotherapy 66 (12): 1545–1555.
Chicago author-date (all authors)
Denies, Sofie, Bregje Leyman, Hanne Huysmans, Francis Combes, Séan Mc Cafferty, Laetitia Cicchelero E, Marjan Steppe, Joyca De Temmerman, and Niek Sanders. 2017. “Evaluation of a Xenogeneic Vascular Endothelial Growth Factor-2 Vaccine in Two Preclinical Metastatic Tumor Models in Mice.” Cancer Immunology Immunotherapy 66 (12): 1545–1555.
Vancouver
1.
Denies S, Leyman B, Huysmans H, Combes F, Mc Cafferty S, Cicchelero E L, et al. Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice. CANCER IMMUNOLOGY IMMUNOTHERAPY. 2017;66(12):1545–55.
IEEE
[1]
S. Denies et al., “Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice,” CANCER IMMUNOLOGY IMMUNOTHERAPY, vol. 66, no. 12, pp. 1545–1555, 2017.
@article{8578973,
  abstract     = {In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor. The tumor growth, survival, and development of an immune response were followed. The cellular immune response was measured by a bioluminescence-based cytotoxicity assay with vascular endothelial growth factor-2 (VEGFR-2)-expressing target cells. Humoral immune responses were quantified by enzyme-linked immunosorbent assay (ELISA). Ex vivo bioluminescence imaging and immunohistological observation of organs were used to detect (micro)metastases. A cellular and humoral immune response was present in prophylactically and therapeutically vaccinated mice, in both tumor models. Nevertheless, survival in prophylactically vaccinated mice was only moderately increased, and no beneficial effect on survival in therapeutically vaccinated mice could be demonstrated. An influx of CD3+ cells and a slight decrease in VEGFR-2 were noticed in the tumors of vaccinated mice. Unexpectedly, the vaccine caused an increased quantity of early micrometastases in the liver. Lung metastases were not increased by the vaccine. These early liver micrometastases did however not grow into macroscopic metastases in either control or vaccinated mice when allowed to develop further after surgical removal of the primary tumor.},
  author       = {Denies, Sofie and Leyman, Bregje and Huysmans, Hanne and Combes, Francis and Mc Cafferty, Séan and Cicchelero, Laetitia and Steppe, Marjan and De Temmerman, Joyca and Sanders, Niek},
  issn         = {0340-7004},
  journal      = {CANCER IMMUNOLOGY IMMUNOTHERAPY},
  keywords     = {Breast cancer,DNA vaccination,Melanoma,Metastasis,VEGFR-2,THERAPEUTIC CANCER VACCINES,DNA VACCINE,GENE-THERAPY,MOUSE MODEL,ANTITUMOR IMMUNITY,DISTANT METASTASIS,ANTI-ANGIOGENESIS,COLORECTAL-CANCER,FACTOR RECEPTOR-2,CELL},
  language     = {eng},
  number       = {12},
  pages        = {1545--1555},
  title        = {Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice},
  url          = {http://dx.doi.org/10.1007/s00262-017-2046-3},
  volume       = {66},
  year         = {2017},
}
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