title: A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.
abstract: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder.
  
  
  
  Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety.
  
  
  
  S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide.
  
  
  
  S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder.
  
  
  
  JapicCTI-090980.
authors.affiliation: Department of Urology, Iwate medical University School of Medicine, Morioka, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Obara
authors.affiliation: Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Eto
authors.affiliation: Department of Urology, Oita University Faculty of Medicine, Yufu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mimata
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kohri
authors.affiliation: Department of Urology, Kure Kyosai Hospital, Kure, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mitsuhata
authors.affiliation: Department of Urology, Shonan Kamakura General Hospital, Kanagawa, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Miura
authors.affiliation: Department of Urology, Kochi University, Nankoku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shuin
authors.affiliation: Department of Urology, Graduate school of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koie
authors.affiliation: Urology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujimoto
authors.affiliation: Department of Urology, Hokkaido Cancer Center, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Minami
authors.affiliation: Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Urology, Tokuyama Central Hospital, Syunan, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nasu
authors.affiliation: Department of Urology, Shonan Fujisawa Tokushukai Hospital, Fujisawa, USA.
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Urology, Graduate school of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, USA.
authors.forename: H
authors.initials: H
authors.lastname: Fuse
authors.affiliation: Department of Urology, Wakayama Medical University, Wakayama, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Hara
authors.affiliation: Shionogi Co. Ltd, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Shionogi Co. Ltd, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Arimura
authors.affiliation: Department of Urology, Iwate medical University School of Medicine, Morioka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujioka
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D059871:HLA-A24 Antigen / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000628:therapy*; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; C000617980:S-288310; D022223:Vaccines, Subunit
keywords: DEPDC1; MPHOSPH1; S-288310; bladder cancer; immunotherapy; peptide vaccine