title: Vaccination of patients with cutaneous melanoma with telomerase-specific peptides.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These results demonstrate that immunity to hTERT can be generated safely and effectively in patients with advanced melanoma and therefore encourage further trials.
authors.affiliation: Department of Dermatology, University of Berne, Switzerland. robert.hunger@insel.ch
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hunger
authors.forename: Kristin
authors.initials: K
authors.lastname: Kernland Lang
authors.forename: Carrie J
authors.initials: CJ
authors.lastname: Markowski
authors.forename: Sissel
authors.initials: S
authors.lastname: Trachsel
authors.forename: Mona
authors.initials: M
authors.lastname: Møller
authors.forename: Jon A
authors.initials: JA
authors.lastname: Eriksen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Rasmussen
authors.forename: Lasse R
authors.initials: LR
authors.lastname: Braathen
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019098:Telomerase / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; C509186:TERT protein, human; D019098:Telomerase