Phase I clinical study of anti-apoptosis protein survivin-derived peptide vaccination for patients with advanced or recurrent urothelial cancer.
Survivin, a member of the inhibitor of apoptosis protein family, is expressed in many malignant tumors including urothelial cancer but is hardly detectable in normal, differentiated adult tissues. Previously we reported CD8-positive cytotoxic T-lymphocytes (CTLs) were successfully induced by stimulation with survivin-2B80-88 peptide in vitro. We started a phase I clinical study of survivin-2B80-88 peptide vaccination for advanced urothelial cancer patients to assess the safety and efficacy of this vaccination. Nine patients were received vaccination and were evaluated for immunological evaluation, adverse events, and clinical responses. A total of 46 vaccinations were carried out. There was no severe adverse event. HLA-A24/survivin-2B80-88 peptide tetramer analysis revealed a significant increase in the peptide-specific CTL frequency after the vaccination in five patients. Slight reduction of the tumor volume was observed in one patient. Survivin-2B80-88 peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in urothelial cancer patients.
Honma
Ichiya
I
Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan. ichiya@sapmed.ac.jp
Kitamura
Hiroshi
H
Torigoe
Toshihiko
T
Takahashi
Akari
A
Tanaka
Toshiaki
T
Sato
Eiji
E
Hirohashi
Yoshihiko
Y
Masumori
Naoya
N
Tsukamoto
Taiji
T
Sato
Noriyuki
N
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000276:immunology*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014057:Tomography, X-Ray Computed; D014516:Ureteral Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D000077022:Survivin