title: A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic renal cell carcinoma.
abstract: BACKGROUND
  Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the von Hippel-Lindau (VHL) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.
  
  
  METHODS
  Six patients with advanced RCC and mutated VHL genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.
  
  
  RESULTS
  Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.
  
  
  CONCLUSIONS
  The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials.
  
  
  BACKGROUND
  98C0139.
authors.affiliation: Vaccine Branch, NCI, NIH, Bethesda, MD, USA. rahmaoe@mail.nih.gov
authors.forename: Osama E
authors.initials: OE
authors.lastname: Rahma
authors.forename: Ed
authors.initials: E
authors.lastname: Ashtar
authors.forename: Ramy
authors.initials: R
authors.lastname: Ibrahim
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Barry
authors.initials: B
authors.lastname: Gause
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Herrin
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Frank
authors.initials: F
authors.lastname: Grollman
authors.forename: George
authors.initials: G
authors.lastname: Grimes
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Bernstein
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D010865:Pilot Projects; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D010455:Peptides; D051794:Von Hippel-Lindau Tumor Suppressor Protein