Adenovirus vector carrying REIC/DKK-3 gene

Neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy

H. Kumon, Y. Ariyoshi, K. Sasaki, T. Sadahira, Motoo Araki, S. Ebara, Hiroyuki Yanai, Masami Watanabe, Yasutomo Nasu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 Kattan'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 × 10 10, 1.0 × 10 11 and 1.0 × 10 12 viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 × 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+3.

Original languageEnglish
Pages (from-to)400-409
Number of pages10
JournalCancer Gene Therapy
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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Prostatectomy
Adenoviridae
Prostatic Neoplasms
Injections
Virion
Genes
Tumor-Infiltrating Lymphocytes
Recurrence
Nomograms
Aspartate Aminotransferases
Alanine Transaminase
Genetic Therapy
Neoplasms
Fever
Safety
Survival
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Adenovirus vector carrying REIC/DKK-3 gene : Neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy. / Kumon, H.; Ariyoshi, Y.; Sasaki, K.; Sadahira, T.; Araki, Motoo; Ebara, S.; Yanai, Hiroyuki; Watanabe, Masami; Nasu, Yasutomo.

In: Cancer Gene Therapy, Vol. 23, No. 11, 01.11.2016, p. 400-409.

Research output: Contribution to journalArticle

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