title: Effective induction of cytotoxic T cells recognizing an epitope peptide derived from hypoxia-inducible protein 2 (HIG2) in patients with metastatic renal cell carcinoma.
abstract: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC.
  
  
  
  Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study. The patients received subcutaneous administration of the peptide as an emulsion form with Montanide ISA-51 VG once a week in a dose-escalation manner (doses of 0.5, 1.0, or 3.0 mg/body, 3 patients for each dose). The primary endpoint was safety, and the secondary endpoints were immunological and clinical responses.
  
  
  
  Vaccinations with HIG2-9-4 peptide could be well tolerated without any serious systemic adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses were detected in eight of the nine patients. Doses of 1.0 or 3.0 mg/body seemed to induce a CTL response better than did a dose of 0.5 mg/body, although the number of patients was too small to draw a firm conclusion. The disease control rate (stable disease for ≥4 months) was 77.8 %, and the median progression-free survival time was 10.3 months.
  
  
  
  HIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising.
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan. watao@iwate-med.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Obara
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Karashima
authors.affiliation: Division of Cell Biology, Biomedical Research Center, Graduated School of Medicine, Juntendo University, Tokyo, Japan.|Department of Biofunctional Micribiota, Graduated School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Renpei
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Kanehira
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takata
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
authors.affiliation: Department of Urology, Kochi Medical School, Kochi, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; C405620:HILPDA protein, human; D009363:Neoplasm Proteins; D022223:Vaccines, Subunit
keywords: Cancer peptide vaccine; Cytotoxic T lymphocyte; Genome-wide expression profile; Renal cell carcinoma