期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 62, 期 2, 页码 75-83出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2011.02.001
关键词
Cutaneous T cell lymphoma (CTCL); GV1001; Tumor vaccination; Telomerase; hTERT-specific peptide vaccination; Regulatory T cells (Treg); Skin-homing receptors; CCR4; CCR6; Granulocyte-monocyte colony stimulating factor (GM-CSF)
类别
资金
- Bernese Cancer League
- Hans Stettler Foundation
- Bernese League against Cancer
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. (C) 2011 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.
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