Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

  • Robert E. Hunger
  • Kristin Kernland Lang
  • Carrie J. Markowski
  • Sissel Trachsel
  • Mona Møller
  • Jon A. Eriksen
  • Anne-Marie Rasmussen
  • Lasse R. Braathen
  • Gustav Gaudernack
Original article

Abstract

Purpose

A phase I study was conducted to investigate the safety, tolerability, and immunological responses to vaccination with a combination of telomerase-derived peptides GV1001 (hTERT: 611–626) and p540 (hTERT: 540–548) using granulocyte–macrophage colony-stimulating factor (GM-CSF) or tuberculin as adjuvant in patients with cutaneous melanoma.

Experimental design

Ten patients with melanoma stages UICC IIb-IV were vaccinated 8 times intradermally with either 60 or 300 nmole of GV1001 and p540 peptide using GM-CSF as adjuvant. A second group of patients received only 300 nmole GV1001 in combination with tuberculin PPD23 injections. HLA typing was not used as an inclusion criterion. Peptide-specific immune responses were measured by delayed-type hypersensitivity (DTH) reactions, in vitro T cell proliferation assays, and cytotoxicity (51-Chromium release) assays for a selected number of clones subsequently generated.

Results

Vaccination was well tolerated in all patients. Peptide-specific immune response measured by DTH reactions and in vitro response could be induced in a dose-dependent fashion in 7 of 10 patients. Cloned T cells from the vaccinated patients showed proliferative responses against both vaccine peptides GV1001 and p540. Furthermore, T cell clones were able to specifically lyse p540-pulsed T2 target cells and various pulsed and unpulsed tumor cell lines.

Conclusion

These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trials.

Keywords

hTERT Telomerase Melanoma Cytotoxic T cells Vaccination Immunotherapy 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Robert E. Hunger
    • 1
  • Kristin Kernland Lang
    • 1
  • Carrie J. Markowski
    • 2
  • Sissel Trachsel
    • 2
  • Mona Møller
    • 3
  • Jon A. Eriksen
    • 3
  • Anne-Marie Rasmussen
    • 2
  • Lasse R. Braathen
    • 1
  • Gustav Gaudernack
    • 2
  1. 1.Department of DermatologyUniversity of Berne, InselspitalBerneSwitzerland
  2. 2.Section for Immunotherapy, Department of ImmunologyOslo University Hospital-Radiumhospitalet and University of OsloOsloNorway
  3. 3.PorsgrunnNorway

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