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A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study

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Abstract

We have previously shown in mice that vaccination with three Her-2-peptides representing B-cell epitopes of the extracellular domain of Her-2/neu induces Her-2/neu-specific IgG antibodies with strong anti-tumor activity in vitro and in vivo. We have now finalized a phase I clinical trial with an anti-Her-2/neu vaccine-construct of immunopotentiating reconstituted influenza virosomes with the three peptides in patients with metastatic breast cancer (MBC). Ten MBC patients with low protein overexpression of Her-2/neu of MBC (+ or ++ upon immunohistochemistry, FISH negative) and positive hormone receptor status were enrolled in a single center phase I study. The virosomal formulated vaccine, consisting of 10 μg/peptide, was intramuscularly applied three times on days 1, 28, and 56. The primary endpoint of the study, which lasted 12 weeks, was safety, the secondary endpoint immunogenicity. Local erythema at the injection site was the only vaccine-related side effect occurring in four patients. In 8 of 10 patients an increase in peptide-specific antibody titer measured by ELISA was found. Importantly, the induced antibodies were also directed against the native Her-2/neu protein. Cellular immune responses, as measured by in vitro production of IL-2, IFN-γ, and TNF-α of PBMCs showed a marked increase after vaccination in the majority of vaccinees. Notably, the number of CD4+CD25+Foxp3+T regulatory cells, which were significantly increased compared to healthy controls prior to vaccination, was markedly reduced following vaccination. In all, the immunological responses after vaccination indicated that the patients in stage IV of disease were immunocompetent and susceptible to vaccination. The Her-2/neu multipeptide vaccine was safe, well tolerated and effective in overcoming immunological tolerance to Her-2/neu. The induction of anti-Her-2-specific antibodies could result in clinical benefit comparable to passive anti-Her-2 antibody therapy.

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Acknowledgments

The study was supported by a grant from BioLife Science and by the Medical University of Vienna. The assistance of Mrs Marika Rosner as study nurse during the phase I clinical trial is very much appreciated.

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Authors and Affiliations

  1. Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Kinderspitalgasse 15, 1090, Vienna, Austria

    Ursula Wiedermann, J. Jasinska, E. Garner-Spitzer & O. Scheiner

  2. Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria

    C. Wiltschke, R. Bartsch, G. Steger & C. C. Zielinski

  3. Department of Environmental Medicine, Medical University of Vienna, Vienna, Austria

    M. Kundi

  4. Pevion Biotech LTD, Bern, Switzerland

    R. Zurbriggen

  5. Department of Dermatology, Medical University of Vienna, Vienna, Austria

    H. Pehamberger

  6. BioLife Science, Vienna, Austria

    J. Jasinska, H. Pehamberger, O. Scheiner & C. C. Zielinski

Authors
  1. Ursula Wiedermann
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  2. C. Wiltschke
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  3. J. Jasinska
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  4. M. Kundi
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  5. R. Zurbriggen
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  6. E. Garner-Spitzer
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  7. R. Bartsch
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  8. G. Steger
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  9. H. Pehamberger
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  10. O. Scheiner
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  11. C. C. Zielinski
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Corresponding author

Correspondence to Ursula Wiedermann.

Additional information

U. Wiedermann and C. Wiltschke contributed equally to this work.

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Wiedermann, U., Wiltschke, C., Jasinska, J. et al. A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Res Treat 119, 673–683 (2010). https://doi.org/10.1007/s10549-009-0666-9

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  • DOI: https://doi.org/10.1007/s10549-009-0666-9

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