Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma.

Abstract

BACKGROUND:

There is currently no curative therapy for cutaneous T cell lymphoma (CTCL). New therapies are therefore needed. Telomerase, the enzyme that allows for unrestricted cell divisions of cancer cells, is a promising target for cancer therapy. The telomerase-specific peptide vaccination GV1001 has shown promising results in previous studies. Since telomerase is expressed in malignant cells of CTCL, GV1001 vaccination in CTCL is a promising new therapeutic approach.

OBJECTIVE:

We sought to investigate the efficacy of GV1001 vaccination in CTCL patients and characterize the induced immune response.

METHODS:

Six CTCL patients were vaccinated with the GV-peptide using granulocyte/macrophage colony-stimulating factor as adjuvant. Objective clinical response and the T cell response were assessed.

RESULTS:

None of the patients demonstrated objective clinical response to the vaccination whereas one patient showed disease progression. 1/6 patients acquired a GV1001-specifc T cell response with a Th1 cytokine profile and expression of skin-homing receptors. This hTERT-specific T cell response was not associated with beneficial modulation of the tumor-infiltrating leukocytes. Furthermore, removal of regulatory T cells did not enhance responsiveness to GV1001 in vitro in any of the patients analyzed.

CONCLUSIONS:

Our results suggest that the GV1001 vaccination is not effective in CTCL patients and disease progression in 1/6 patients raises concerns about its safety. By analyzing skin-homing properties of GV1001-specific T cells and the involvement of regulatory T cells we nevertheless provide insight into vaccine-induced immune responses which may help to improve vaccine strategies in CTCL.

• Authors: Christoph Schlapbach, Daniel Yerly, Barbara Daubner, Nikhil Yawalkar, Robert E Hunger
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 62 Issue 2 Pg. 75-83 (May 2011) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 21377838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier Ireland Ltd.

Chemical References

• Cancer Vaccines
• Peptide Fragments
• Peptides
• Vaccines, Subunit
• Granulocyte-Macrophage Colony-Stimulating Factor
• GV1001 peptide
• Telomerase

Topics

• Adult
• Aged
• Aged, 80 and over
• Cancer Vaccines (therapeutic use)
• Disease Progression
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Immune System
• Lymphoma, T-Cell, Cutaneous (therapy)
• Male
• Middle Aged
• Peptide Fragments (metabolism)
• Peptides (chemistry)
• Telomerase (metabolism)
• Treatment Outcome
• Vaccines, Subunit (therapeutic use)