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 language | English |
|---|---|
| Pages (from-to) | 400-409 |
| Number of pages | 10 |
| Journal | Cancer Gene Therapy |
| Volume | 23 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Adenovirus vector carrying REIC/DKK-3 gene
T2 - Neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy
AU - Kumon, H.
AU - Ariyoshi, Y.
AU - Sasaki, K.
AU - Sadahira, T.
AU - Araki, Motoo
AU - Ebara, S.
AU - Yanai, Hiroyuki
AU - Watanabe, Masami
AU - Nasu, Yasutomo
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84992124445&partnerID=8YFLogxK
U2 - 10.1038/cgt.2016.53
DO - 10.1038/cgt.2016.53
M3 - Article
VL - 23
SP - 400
EP - 409
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 11
ER -