title: 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.affiliation: Department of Urology, Kurume University School of Medicine, Fukuoka 830-0011, Japan. suekane@med.kurume-u.ac.jp
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nishitani
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
authors.forename: Takako
authors.initials: T
authors.lastname: Kokubu
authors.forename: Masayasu
authors.initials: M
authors.lastname: Naitoh
authors.forename: Shigenori
authors.initials: S
authors.lastname: Honma
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.forename: Kei
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Kanayama
mesh_terms: D019496:Cancer Vaccines / Q000633:toxicity*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D003131:Combined Modality Therapy; D016207:Cytokines / Q000627:therapeutic use; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018579:Patient Selection; D022223:Vaccines, Subunit / Q000633:toxicity*
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D022223:Vaccines, Subunit