Angiogenesis

, Volume 11, Issue 4, pp 381–393

Anti-tumoral effect of active immunotherapy in C57BL/6 mice using a recombinant human VEGF protein as antigen and three chemically unrelated adjuvants

  • Yanelys Morera
  • Mónica Bequet-Romero
  • Marta Ayala
  • Humberto Lamdán
  • Else-Marie Agger
  • Peter Andersen
  • Jorge V. Gavilondo
Original Paper

Abstract

Following the clinical success of Bevacizumab, a humanized monoclonal antibody that affects the interaction between vascular endothelial growth factor (VEGF) and its receptors, blocking tumor-induced angiogenesis has become one of the most important targets for the development of new cancer therapeutic drugs and procedures. Among the latter, therapeutic vaccination using VEGF as antigen presents itself as very attractive, with the potential of generating not only a growth factor blocking antibody response but also a cellular response against tumor cells and stromal elements, which appear to be a major source of tumor VEGF. In this paper, we report the development of a protein vaccine candidate, based on a human modified VEGF antigen that is expressed at high levels in E. coli. With respect to controls, immunization experiments in C57BL/6 mice using weekly doses of this antigen and three adjuvants of different chemical natures show that time for tumor development after subcutaneous injection of Melanoma B16-F10 cells increases, tumors that develop grow slower, and overall animal survival is higher. Immunization also prevents tumor development in some mice, making them resistant to second tumor challenges. Vaccination of mice with the human modified VEGF recombinant antigen produces antibodies against the human antigen and the homologous mouse VEGF molecule. We also show that sera from immunized mice block human VEGF-induced HUVEC proliferation. Finally, a possible contribution of T cell cytotoxicity to the overall anti-tumor effect is suggested from the results of vaccination experiments where CD8+ lymphocytes were impaired using neutralizing rat antibodies.

Keywords

VEGF Angiogenesis Immunotherapy Vaccine Cancer VEGFR2 

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Yanelys Morera
    • 1
  • Mónica Bequet-Romero
    • 1
  • Marta Ayala
    • 1
  • Humberto Lamdán
    • 1
  • Else-Marie Agger
    • 2
  • Peter Andersen
    • 2
  • Jorge V. Gavilondo
    • 1
  1. 1.Recombinant Antibody Group, Cancer Research DepartmentCenter for Genetic Engineering and BiotechnologyPlaya, HavanaCuba
  2. 2.Statens Serum InstituteCopenhagenDenmark

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