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Molecular Medicine

, Volume 18, Issue 12, pp 1499–1508 | Cite as

High Immune Response Rates and Decreased Frequencies of Regulatory T Cells in Metastatic Renal Cell Carcinoma Patients after Tumor Cell Vaccination

  • Heike Pohla
  • Alexander Buchner
  • Birgit Stadlbauer
  • Bernhard Frankenberger
  • Stefan Stevanovic
  • Steffen Walter
  • Ronald Frank
  • Tim Schwachula
  • Sven Olek
  • Joachim Kopp
  • Gerald Willimsky
  • Christian G Stief
  • Alfons Hofstetter
  • Antonio Pezzutto
  • Thomas Blankenstein
  • Ralph Oberneder
  • Dolores J Schendel
Research Article

Abstract

Our previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well tolerated and feasible in metastatic renal cell carcinoma (RCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs). An overall immune response capacity to virus-derived control peptides was present in 100% of patients before vaccination. Vaccine-induced immune responses to tumor-associated antigens occurred in 75% of patients, demonstrating the potent immune stimulatory capacity of this generic vaccine. Furthermore, some patients reacted to peptide epitopes of antigens not expressed by the vaccine, showing that epitope-spreading occurred in vivo. Frequencies of nTregs and MDSCs were comparable to healthy donors at the beginning of study. A significant decrease of nTregs was detected after vaccination (p = 0.012). High immune response rates, decreased frequencies of nTregs and a mixed T helper 1/T helper 2 (TH1/TH2)-like cytokine pattern support the applicability of this RCC generic vaccine for use in combination therapies.

Notes

Acknowledgments

The authors thank Heidi Herbig and Adam Slusarski for excellent technical support. The study was funded by the Federal Ministry of Education and Research (01 GE 9624/1) and the German National Research Foundation (SFB-455 and SFB-TR36).

Supplementary material

10020_2012_18121499_MOESM1_ESM.pdf (3.7 mb)
High Immune Response Rates and Decreased Frequencies of Regulatory T Cells in Metastatic Renal Cell Carcinoma Patients after Tumor Cell Vaccination

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© The Author(s) 2012

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Authors and Affiliations

  • Heike Pohla
    • 1
    • 2
  • Alexander Buchner
    • 1
    • 3
  • Birgit Stadlbauer
    • 1
  • Bernhard Frankenberger
    • 2
  • Stefan Stevanovic
    • 4
  • Steffen Walter
    • 5
  • Ronald Frank
    • 6
  • Tim Schwachula
    • 7
  • Sven Olek
    • 7
  • Joachim Kopp
    • 8
  • Gerald Willimsky
    • 9
    • 10
  • Christian G Stief
    • 1
    • 3
  • Alfons Hofstetter
    • 1
    • 3
  • Antonio Pezzutto
    • 8
    • 11
  • Thomas Blankenstein
    • 9
    • 10
  • Ralph Oberneder
    • 3
    • 12
  • Dolores J Schendel
    • 2
  1. 1.Laboratory of Tumor Immunology, LIFE CenterLudwig Maximilians UniversityMünchenGermany
  2. 2.Institute of Molecular Immunology, Helmholtz Zentrum MünchenGerman Research Center for Environmental Health, and Clinical Cooperation Group “Immune Monitoring”MunichGermany
  3. 3.Department of UrologyLudwig Maximilians UniversityMunichGermany
  4. 4.Department of ImmunologyEberhard Karls UniversityTübingenGermany
  5. 5.Immatics BiotechnologiesTübingenGermany
  6. 6.Department of Chemical BiologyHelmholtz Centre for Infection ResearchBraunschweigGermany
  7. 7.EpiontisBerlinGermany
  8. 8.Department of Hematology, Oncology and ImmunologyCharité University MedicineBerlinGermany
  9. 9.Institute of ImmunologyCharité University of MedicineBerlinGermany
  10. 10.Max-Delbrück CenterCharité University MedicineBerlinGermany
  11. 11.Department of Hematology, Oncology and Tumor ImmunologyCharité University MedicineBerlinGermany
  12. 12.Urological Clinic Munich-PlaneggPlaneggGermany

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