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Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin

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Abstract

Purpose: As prognosis of advanced pancreatic cancer remains gloomy, novel therapeutic modalities have to be developed. Immunotherapy, which targets tumor-associated antigens of tumor cells or tumor stroma, is currently under investigation. As survivin is expressed by neoplastic and tumor endothelial cells, but rarely by normal cells, this antigen appears as an intriguing target molecule. Methods: A 72-year old patient, suffering from pancreatic cancer refractory to gemcitabine therapy, received the survivin-based peptide vaccinations consisting of 100 μg of a modified HLA-A2 restricted survivin96–104 epitope in Montanide®. Each visit the patient was assessed for adverse events, quality of life and immunological response. Immunemonitoring was performed by IFN-γ-ELISPOT analysis of peripheral blood lymphocytes. Clinical outcome was evaluated by repetitive computed tomography. Results: Under vaccination with survivin peptides the patient initially underwent partial remission of liver metastasis which proceeded after 6 months into a complete remission with a duration of 8 months. Immunological monitoring revealed strong vaccine-induced immune-reactivity against survivin. Unfortunately, after the patient was weaned from vaccination in state of no evidence of disease, he developed recurrent disease. Conclusion: T-cell responses against survivin-expressing cells of the tumor itself and tumor endothelium should impact tumor growth and metastasis. The presented patient with pancreatic cancer is the first example of a successful application of a survivin-based vaccination in the clinical setting. An ongoing phase I/II trial with HLA-A1, -A2 and -B35 restricted survivin peptides for patients with advanced cancer will provide further information towards this notion.

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Acknowledgments

The authors are grateful to Prof. Dr. S. Delorme, Department of Radiology, University of Heidelberg, Germany, for his critical review of the radiological images. We are further indebted to Marianne Berwick and Per thor Straten for helpful discussions during preparation of the manuscript as well as Brigitte Bauer for her excellent data managing. The clinical trial was supported in part by the Deutsche Forschungsgemeinschaft (DFG) grant KFO-124/1-1.

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Authors and Affiliations

  1. Department of Dermatology and Venerology, University of Wuerzburg, Josef-Schneider-Strasse 2, Building 13, 97080, Wuerzburg, Germany

    Marion Wobser, Petra Keikavoussi & Juergen C. Becker

  2. Department of Internal Medicine, University of Wuerzburg, Wuerzburg, Germany

    Volker Kunzmann

  3. Department of Radiology, University of Wuerzburg, Wuerzburg, Germany

    Markus Weininger

  4. Tumor immunology group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark

    Mads H. Andersen

Authors
  1. Marion Wobser
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  2. Petra Keikavoussi
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  3. Volker Kunzmann
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  4. Markus Weininger
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  5. Mads H. Andersen
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  6. Juergen C. Becker
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Corresponding author

Correspondence to Juergen C. Becker.

Additional information

The clinical trial was supported in part by the Deutsche Forschungsgemeinschaft (DFG) grant KFO-124/1-1. The clinical trial was approved by the local ethical committee and informed consent was obtained from each patient. Human investigations were performed in accordance with an assurance filed with and approved by the Department of Health and Human Services.

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Wobser, M., Keikavoussi, P., Kunzmann, V. et al. Complete remission of liver metastasis of pancreatic cancer under vaccination with a HLA-A2 restricted peptide derived from the universal tumor antigen survivin. Cancer Immunol Immunother 55, 1294–1298 (2006). https://doi.org/10.1007/s00262-005-0102-x

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  • DOI: https://doi.org/10.1007/s00262-005-0102-x

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