Breast Cancer Research and Treatment

, Volume 106, Issue 1, pp 29–38 | Cite as

Delayed tumor onset and reduced tumor growth progression after immunization with a Her-2/neu multi-peptide vaccine and IL-12 in c-neu transgenic mice

  • Stefan Wagner
  • Joanna Jasinska
  • Heimo Breiteneder
  • Michael Kundi
  • Hubert Pehamberger
  • Otto Scheiner
  • Christoph C. Zielinski
  • Ursula Wiedermann
Preclinical Study

Abstract

Passive immunotherapy with monoclonal antibodies is a routinely performed but cost intensive treatment against certain cancers. Induction of humoral anti-tumor responses by active peptide immunization has therefore become a favorable treatment concept. We have recently identified three peptides representing B-cell epitopes of the extracellular domain of Her-2/neu each of them inducing Her-2/neu specific immune responses with anti-tumor activity in vitro. The present study was performed to evaluate the in vivo protective capacity of a combined vaccination with these three peptides in FVB/N transgenic mice spontaneously developing c-neu overexpressing breast cancers. The three Her-2/neu peptides coupled to tetanus toxoid were administered with or without addition of recombinant IL-12. At the time all untreated mice had developed tumors about 40% of peptide-immunized mice and nearly 60% of mice immunized with the peptide vaccine co-applied with IL-12 remained tumor free. Moreover, co-administration of IL-12 had a significant impact on the retardation of tumor progression. The enhanced anti-tumor efficacy of the vaccine by IL-12 was associated with a Th1 biased immune response as demonstrated by an increased IFN-γ production in vitro and elevated Her-2-specific IgG levels. Our findings clearly demonstrate that this multi-peptide vaccine is effective in tumor prevention and support its use against minimal disease, drug-resistant tumors or even for prophylaxis against cancers overexpressing Her-2/neu.

Keywords

Her-2/neu Transgenic mice Peptide vaccination Antibodies Tumor prevention IL-12 Th1 

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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Stefan Wagner
    • 1
    • 6
  • Joanna Jasinska
    • 2
    • 6
  • Heimo Breiteneder
    • 1
    • 7
  • Michael Kundi
    • 3
  • Hubert Pehamberger
    • 4
    • 7
  • Otto Scheiner
    • 1
    • 7
  • Christoph C. Zielinski
    • 5
    • 7
  • Ursula Wiedermann
    • 2
  1. 1.Department of Pathophysiology, Center for Physiology and PathophysiologyMedical University of ViennaViennaAustria
  2. 2.Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and PathophysiologyMedical University of ViennaViennaAustria
  3. 3.Department of Environmental HealthMedical University of ViennaViennaAustria
  4. 4.Department of DermatologyMedical University of ViennaViennaAustria
  5. 5.Clinical Division of Oncology, Department of Medicine IMedical University of ViennaViennaAustria
  6. 6.BioLife ScienceViennaAustria
  7. 7.Center of Excellence in Clinical and Experimental Oncology, Medical University of ViennaViennaAustria

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