, Volume 10, Issue 1, pp 23–34 | Cite as

Prophylactic naked DNA vaccination with the human vascular endothelial growth factor induces an anti-tumor response in C57Bl/6 mice

  • Mónica Bequet-Romero
  • Marta Ayala
  • Boris E. Acevedo
  • Ernesto Galbán Rodríguez
  • Omar López Ocejo
  • Isis Torrens
  • Jorge V. Gavilondo
Original Paper


Passive immunotherapy against soluble pro-angiogenic factors and/or their receptors in endothelial cells has become a promising approach in cancer therapeutics. There is also experimental evidence indicating that an active immunotherapy strategy directed towards these target molecules could also be effective. In this paper we show that it is possible to reduce tumor growth or increase the survival of tumor-bearing C57Bl/6 mice when animals are vaccinated with the human vascular endothelial growth factor (VEGF) isoform 121 gene (hVEGF121), and later challenged with melanoma or lung carcinoma tumor cells. Immunization was done with 10 μg DNA doses of the hVEGF121 gene, which is highly homologous to its mouse counterpart, administered on a weekly basis using a plasmid bearing 5 CpG bacterial motifs. Histopathology analyses of tumors of hVEGF121 immunized animals showed a decrease in tumor cell density around vessels and in mitotic figures, as well as an increase in apoptotic tumor cells. A statistically significant cell cytotoxic response was found when spleen cells of immunized mice were co-cultured in vitro with mouse tumor VEGF-producing cells. Vaccination with an hVEGF121 gene mutated to make it deficient for VEGF receptor binding, produced similar in vitro and in vivo results, and significantly reduced the number of spontaneous metastases produced by the mouse Lewis lung carcinoma. Our results indicate that human VEGF DNA can be employed for anti-angiogenic active immunotherapy in mice, and that direct cell cytotoxicity is a contributor mechanism to the overall anti-tumor effects seen in immunized animals.


Angiogenesis Cancer Immunotherapy VEGF DNA immunization 



We thank Y. Soria for excellent technical assistance in animal handling and A. Vásquez for the histopathology analyses. We are also grateful to Dr. T. C. Wu for providing the TC-1 carcinoma model.


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Copyright information

© Springer Science + Business Media B.V. 2007

Authors and Affiliations

  • Mónica Bequet-Romero
    • 1
  • Marta Ayala
    • 1
  • Boris E. Acevedo
    • 1
  • Ernesto Galbán Rodríguez
    • 2
  • Omar López Ocejo
    • 1
  • Isis Torrens
    • 1
  • Jorge V. Gavilondo
    • 1
  1. 1.Recombinant Antibodies Laboratory, Cancer Research DepartmentCenter for Genetic Engineering and BiotechnologyHavanaCuba
  2. 2.Vaccine DivisionCenter for Genetic Engineering and BiotechnologyHavanaCuba

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