Phase I trial of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients.

Abstract

The aim of this clinical trial was to investigate the toxicity and immunological responses of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Patients were confirmed to be human leukocyte antigen (HLA)-A24 or HLA-A2 positive and had histologically confirmed renal cell carcinoma. Ten patients were enrolled in the present study. The peptides to be administered were determined based on the presence of peptide-specific cytotoxic T lymphocyte precursors in peripheral blood mononuclear cells (PBMC) and peptide-specific IgG in the plasma of cancer patients. Patients received subcutaneous injections of four different peptides (3 mg/peptide) every 2 weeks. Vaccinations were well tolerated without any major adverse events. A minimal increase in peptide-specific interferon-gamma production in postvaccination PBMC was observed, regardless of higher levels of cytotoxic T lymphocyte activity in prevaccination PBMC. In contrast, an increase in peptide-specific IgG levels of postvaccination (sixth) plasma was observed in the majority of patients. After progression, five patients received interleukin-2 therapy and continuous vaccination, with survival of 31, 25, 23, 17, and 15 months, but interleukin-2 did not impede humoral responses boosted by the vaccination. These results encourage further clinical trials of personalized peptide vaccinations.

• Authors: Shigetaka Suekane, Masaaki Nishitani, Masanori Noguchi, Yoshihiro Komohara, Takako Kokubu, Masayasu Naitoh, Shigenori Honma, Akira Yamada, Kyogo Itoh, Kei Matsuoka, Hiroomi Kanayama
• Journal: Cancer science (Cancer Sci) Vol. 98 Issue 12 Pg. 1965-8 (Dec 2007) ISSN: 1349-7006 [Electronic] England
• PMID: 17919310 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Cytokines
• HLA-A Antigens
• HLA-A2 Antigen
• HLA-A24 Antigen
• Immunoglobulin G
• Vaccines, Subunit

Topics

• Cancer Vaccines (toxicity)
• Carcinoma, Renal Cell (immunology, pathology)
• Combined Modality Therapy
• Cytokines (therapeutic use)
• HLA-A Antigens (immunology)
• HLA-A2 Antigen (immunology)
• HLA-A24 Antigen
• Humans
• Immunoglobulin G (blood)
• Kidney Neoplasms (immunology, pathology)
• Neoplasm Metastasis
• Neoplasm Staging
• Patient Selection
• Vaccines, Subunit (toxicity)