1275 PHASE I CLINICAL TRIAL OF NOVEL CDCA1 DERIVED EPITOPE PEPTIDE VACCINE THERAPY FOR CASTRATION-RESISTANT PROSTATE CANCER (2011)

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111275 PHASE I CLINICAL TRIAL OF NOVEL CDCA1 DERIVED EPITOPE PEPTIDE VACCINE THERAPY FOR CASTRATION-RESISTANT PROSTATE CANCER Wataru Obara, Fuminori Sato, Koji Yoshida, Takuya Tsunoda, Kazuhiro Iwasaki, Ryo Takata, Hiromitsu Mimata, Yusuke Nakamura, and Tomoaki Fujioka Wataru ObaraWataru Obara Morioka, Japan More articles by this author , Fuminori SatoFuminori Sato Oita, Japan More articles by this author , Koji YoshidaKoji Yoshida Tokyo, Japan More articles by this author , Takuya TsunodaTakuya Tsunoda Tokyo, Japan More articles by this author , Kazuhiro IwasakiKazuhiro Iwasaki Morioka, Japan More articles by this author , Ryo TakataRyo Takata Morioka, Japan More articles by this author , Hiromitsu MimataHiromitsu Mimata Oita, Japan More articles by this author , Yusuke NakamuraYusuke Nakamura Tokyo, Japan More articles by this author , and Tomoaki FujiokaTomoaki Fujioka Morioka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.961AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We had previously reported genome-wide expression profile analysis of prostate cancer by means of cDNA microarray and identified cell division cycle associated gene 1 (CDCA1) as a specific onco-gene. We subsequently detected that stimulation using HLA-A2402 restricted CDCA1 derived peptide induce specific cytotoxicic T lymphocyte (CTL). We conducted Phase I clinical trial using this novel peptide vaccine and assessed both the safety and efficacy for patients with castration-resistant prostate cancer (CRPC). METHODS The main eligibility criteria were CRPC patients who were already resistant to the standard androgen deprivation therapy or chemotherapy (docetaxel) and having HLA-A*2402 genotype. Patients were vaccinated on day 1, 8, 15 and 22 of each 28-day treatment cycles. On each vaccination day, 9 mer modified CDCA1 (VYGIRLEHF) peptide emulsified with Montanaide ISA 51 adjuvant were injected by subcutaneously in a dose-escalation manner (doses of 1.0, 3.0 mg/body, 6 patients/1 cohort). The primary end point was evaluation of safety and secondary end point was peptide specific CTL response and overall survival. RESULTS Vaccinations were well tolerated without severe adverse effect of grade 3 or higher. The most common adverse events were grade 1 or 2 skin reactions at the injection sites. Of 12 patients who completed at least one course of the treatment, 8 (66.7%) developed skin reactions. Specific CTLs reacting to CDCA1 epitope peptide were induced 8 (66.7%) patients. The CTL reaction and skin reaction was recognized for synchronization. The median overall survival time was more than 10.3 months. CONCLUSIONS Our experience data suggest that novel CDCA1 epitope peptide vaccine treatment is tolerable and might provide clinical benefit with extension of the overall survival for patients with CRPC resistant to docetaxel. Peptide specific CTLs could be induced by CDCA1 peptide vaccine at a high rate. From an immunological point of view, the optimal dose for further clinical trial might therefore be 3.0 mg/body or higher. This trial was registered with ClinicalTrial.gov (no. NCT 01225471). © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e510 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wataru Obara Morioka, Japan More articles by this author Fuminori Sato Oita, Japan More articles by this author Koji Yoshida Tokyo, Japan More articles by this author Takuya Tsunoda Tokyo, Japan More articles by this author Kazuhiro Iwasaki Morioka, Japan More articles by this author Ryo Takata Morioka, Japan More articles by this author Hiromitsu Mimata Oita, Japan More articles by this author Yusuke Nakamura Tokyo, Japan More articles by this author Tomoaki Fujioka Morioka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...