title: Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens.
abstract: BACKGROUND
  Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK), lymphocyte antigen-6 complex locus K (LY6K), and insulin-like growth factor-II mRNA binding protein-3 (IMP3) had been shown to be promising for esophageal squamous cell carcinoma (ESCC), we further performed a multicenter, non-randomized phase II clinical trial.
  
  
  METHODS
  Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+)) and -negative (24(-)) groups.
  
  
  RESULTS
  The OS in the 24 (+) group (n = 35) tended to be better than that in the 24(-) group (n = 25) (MST 4.6 vs. 2.6 month, respectively, p = 0.121), although the difference was not statistically significant. However, the PFS in the 24(+) group was significantly better than that in the 24(-) group (p = 0.032). In the 24(+) group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+) group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses.
  
  
  CONCLUSIONS
  The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients.
  
  
  BACKGROUND
  ClinicalTrials.gov, number NCT00995358.
authors: First Department of Surgery, University of Yamanashi, Yamanashi, Japan. surkoji@nus.edu.sg
authors: Koji
authors: K
authors: Kono
authors: Hisae
authors: H
authors: Iinuma
authors: Yasunori
authors: Y
authors: Akutsu
authors: Hiroaki
authors: H
authors: Tanaka
authors: Naoko
authors: N
authors: Hayashi
authors: Yasuto
authors: Y
authors: Uchikado
authors: Tsuyoshi
authors: T
authors: Noguchi
authors: Hideki
authors: H
authors: Fujii
authors: Kota
authors: K
authors: Okinaka
authors: Ryoji
authors: R
authors: Fukushima
authors: Hisahiro
authors: H
authors: Matsubara
authors: Masaichi
authors: M
authors: Ohira
authors: Hideo
authors: H
authors: Baba
authors: Shoji
authors: S
authors: Natsugoe
authors: Seigou
authors: S
authors: Kitano
authors: Kazuyoshi
authors: K
authors: Takeda
authors: Koji
authors: K
authors: Yoshida
authors: Takuya
authors: T
authors: Tsunoda
authors: Yusuke
authors: Y
authors: Nakamura
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015166:Monitoring, Immunologic; D009367:Neoplasm Staging; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D010455:Peptides