title: Multiple therapeutic peptide vaccines consisting of combined novel cancer testis antigens and anti-angiogenic peptides for patients with non-small cell lung cancer.
abstract: BACKGROUND
  Vaccine treatment using multiple peptides derived from multiple proteins is considered to be a promising option for cancer immune therapy, but scientific evidence supporting the therapeutic efficacy of multiple peptides is limited.
  
  
  METHODS
  We conducted phase I trials using a mixture of multiple therapeutic peptide vaccines to evaluate their safety, immunogenicity and clinical response in patients with advanced/recurrent NSCLC. We administered two different combinations of four HLA-A24-restricted peptides. Two were peptides derived from vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2), and the third was a peptide derived from up-regulated lung cancer 10 (URLC10, which is also called lymphocyte antigen 6 complex locus K [LY6K]). The fourth peptide used was derived from TTK protein kinase (TTK) or cell division associated 1 (CDCA1). Vaccines were administered weekly by subcutaneous injection into the axillary region of patients with montanide ISA-51 incomplete Freund's adjuvant, until the disease was judged to have progressed or patients requested to be withdrawn from the trial. Immunological responses were primarily evaluated using an IFN-gamma ELiSPOT assay.
  
  
  RESULTS
  Vaccinations were well tolerated with no severe treatment-associated adverse events except for the reactions that occurred at the injection sites. Peptide-specific T cell responses against at least one peptide were observed in 13 of the 15 patients enrolled. Although no patient exhibited complete or partial responses, seven patients (47%) had stable disease for at least 2 months. The median overall survival time was 398 days, and the 1- and 2-year survival rates were 58.3% and 32.8%, respectively.
  
  
  CONCLUSIONS
  Peptide vaccine therapy using a mixture of four novel peptides was found to be safe, and is expected to induce strong specific T cell responses.
  
  
  BACKGROUND
  These studies were registered with ClinicalTrials.gov NCT00633724 and NCT00874588.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Fukuhara
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamaura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mutoh
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Okabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yaginuma
authors.forename: Takeo
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yonechi
authors.forename: Jun
authors.initials: J
authors.lastname: Osugi
authors.forename: Mika
authors.initials: M
authors.lastname: Hoshino
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Higuchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shio
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ise
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007109:Immunity; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D016019:Survival Analysis; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000951:Antigens, Neoplasm; D022223:Vaccines, Subunit