Vaccination of patients with cutaneous melanoma with telomerase-specific peptides.

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.

• Authors: Robert E Hunger, Kristin Kernland Lang, Carrie J Markowski, Sissel Trachsel, Mona Møller, Jon A Eriksen, Anne-Marie Rasmussen, Lasse R Braathen, Gustav Gaudernack
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 60 Issue 11 Pg. 1553-64 (Nov 2011) ISSN: 1432-0851 [Electronic] Germany
• PMID: 21681371 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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