論文

査読有り
2016年11月

Adenovirus vector carrying REICIDKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy

CANCER GENE THERAPY
  • H. Kumon
  • ,
  • Y. Ariyoshi
  • ,
  • K. Sasaki
  • ,
  • T. Sadahira
  • ,
  • M. Araki
  • ,
  • S. Ebara
  • ,
  • H. Yanai
  • ,
  • M. Watanabe
  • ,
  • Y. Nasu

23
11
開始ページ
400
終了ページ
409
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/cgt.2016.53
出版者・発行元
NATURE PUBLISHING GROUP

As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kaftan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11) and 1.0 x 10(12) viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 x 10(12) vp in 3.6 ml (n=6) Was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration With cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+2:

リンク情報
DOI
https://doi.org/10.1038/cgt.2016.53
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000388063700006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1038/cgt.2016.53
  • ISSN : 0929-1903
  • eISSN : 1476-5500
  • Web of Science ID : WOS:000388063700006

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