title: Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer.
abstract: BACKGROUND
  We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.
  
  
  METHODS
  We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1-1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.
  
  
  RESULTS
  In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-gamma responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.
  
  
  CONCLUSIONS
  This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.
authors.affiliation: Dept. of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan. tsuruma@sapmed.ac.jp
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Tsuruma
authors.forename: Yuji
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Tosei
authors.initials: T
authors.lastname: Ohmura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Katsuramaki
authors.forename: Fumitake
authors.initials: F
authors.lastname: Hata
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Furuhata
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Toyota
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Yagihashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Kumiko
authors.initials: K
authors.lastname: Shimozawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Okazaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mizushima
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nomura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000502:physiology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012008:Recurrence; D012698:Serologic Tests; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D000077022:Survivin