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AE37 peptide vaccination in prostate cancer: a 4-year immunological assessment updates on a phase I trial

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Abstract

In our recent phase I trial, we demonstrated that the AE37 vaccine is safe and induces HER-2/neu-specific immunity in a heterogeneous population of HER-2/neu + prostate cancer patients. Herein, we tested whether one AE37 boost can induce long-lasting immunological memory in these patients. Twenty-three patients from the phase I study received one AE37 boost 6-month post-primary vaccinations. Local/systemic toxicities were evaluated following the booster injection. Immunological responses were monitored 1-month (long-term booster; LTB) and 3-year (long-term immunity; LTI) post-booster by delayed-type hypersensitivity, IFN-γ ELISPOT and proliferation assays. Regulatory T cell (Treg) frequencies, plasma transforming growth factor-β (TGF-β) and indoleamine 2,3-deoxygenase (IDO) activity levels were also determined at the same time points. The AE37 booster was safe and well tolerated. Immunological monitoring revealed vaccine-specific long-term immunity in most of the evaluated patients during both LTB and LTI, although individual levels of immunity during LTI were decreased compared with those measured 3 years earlier during LTB. This was paralleled with increased Tregs, TGF-β levels and IDO activity. One AE37 booster generated long-term immunological memory in HER-2/neu + prostate cancer patients, which was detectable 3 years later, albeit with a tendency to decline. Boosted patients had favorable clinical outcome in terms of overall and/or metastasis-free survival compared with historical groups with similar clinical characteristics at diagnosis. We suggest that more boosters and/or concomitant disarming of suppressor circuits may be necessary to sustain immunological memory, and therefore, further studies to optimize the AE37 booster schedule are warranted.

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Acknowledgments

We are indebted to our patients for their voluntary participation in this study. We thank Dr Eric von Hofe for critical reading of the manuscript. We also thank Joanne Kalogeropoulou and Efi Pappou for excellent technical assistance, Dr. Stratos Bissias for helping in patients’ follow-up and C. Zeyher for expert assistance with Trp/Kyn measurements. This study was supported by Antigen Express, Inc. Worcester, Massachusetts, and a grant from OPAP SA to Michael Papamichail.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Building No. 2, 3rd Floor, 171 Alexandras Avenue, 11522, Athens, Greece

    Sonia A. Perez, Eleftheria A. Anastasopoulou, Panagiotis Tzonis, Michail Papamichail & Constantin N. Baxevanis

  2. Department of Immunology, Institute for Cell Biology, Eberhard-Karls University, Tübingen, Germany

    Cécile Gouttefangeas

  3. Interfaculty Institute of Biochemistry, Eberhard-Karls University, Tübingen, Germany

    Hubert Kalbacher

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  1. Sonia A. Perez
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  2. Eleftheria A. Anastasopoulou
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Correspondence to Sonia A. Perez.

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Perez, S.A., Anastasopoulou, E.A., Tzonis, P. et al. AE37 peptide vaccination in prostate cancer: a 4-year immunological assessment updates on a phase I trial. Cancer Immunol Immunother 62, 1599–1608 (2013). https://doi.org/10.1007/s00262-013-1461-3

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