title: A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin.
abstract: OBJECTIVE
  • To investigate the safety and immune responses of 12 consecutive weeks of once-weekly personalized peptide vaccine (PPV) administration in patients with advanced urothelial carcinoma (UC) for whom therapy with methotrexate, vinblastine, adriamycin and cisplatin (MVAC) has failed.
  
  
  METHODS
  • A phase I trial was designed. Ten patients with MVAC-refractory advanced or metastatic UC were treated with weekly personalized peptide vaccine 12 times using positive peptides chosen from 14 and 16 peptides in patients with human leucocyte antigens A24 and A2, respectively. • Peptide-specific cytotoxic T lymphocyte precursor analysis by interferon-γ production and peptide-reactive immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay was monitored during the treatment.
  
  
  RESULTS
  • The peptide vaccination was safe and well tolerated with no major adverse effects. Increased cytotoxic T lymphocyte response and the anti-peptide IgG titre were revealed by the post-vaccination sera in eight patients. • Clinical responses were as follows: one complete response, one partial response, two stable disease and six progressive disease. • Median progression-free survival and overall survival were 3.0 and 8.9 months, respectively. In the four responders, median progression-free survival and overall survival were 21 and 24 months, respectively.
  
  
  CONCLUSIONS
  • This phase I study showed the safety of and boosted immune responses in response to PPV for advanced UC. • The potential efficacy of 12 consecutive weekly vaccinations with PPV in patients with advanced UC merits further investigation based on these findings.
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Takefumi
authors.initials: T
authors.lastname: Satoh
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Tabata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujita
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Iwamura
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.forename: Shiro
authors.initials: S
authors.lastname: Baba
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D012074:Remission Induction / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014057:Tomography, X-Ray Computed; D014571:Urologic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D019496:Cancer Vaccines; D006680:HLA Antigens; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate