Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

Cancer Immunol Immunother. 2011 Nov;60(11):1553-64. doi: 10.1007/s00262-011-1061-z. Epub 2011 Jun 17.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Female
  • Humans
  • Male
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / adverse effects
  • Peptide Fragments / immunology*
  • Peptide Fragments / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Telomerase / adverse effects
  • Telomerase / immunology*
  • Telomerase / therapeutic use*

Substances

  • Cancer Vaccines
  • Peptide Fragments
  • TERT protein, human
  • Telomerase