A phase I/II study of adenovirus-mediated reduced expression in immortalized cells (REIC/DKK-3) gene therapy for prostate cancer: An interim report.

Abstract

161 Background: A new cancer therapeutic gene; REIC/Dkk-3 was found in Okayama university in 2000. In vivo experiments have demonstrated outstanding cancer-selective apoptosis effects and anti-cancer immunoactivity against various types of malignant tumors. With these positive experimental results, a phase I/II study of adenovirus-mediated REIC/Dkk-3 gene therapy for prostate cancer was initiated from January 2011 in Okayama university hospital. Methods: Two major inclusion criteria category were set up; A: A recurrence of prostate cancer following definitive endocrine therapy with/without metastasis, B: A localized prostate cancer which was considered high risk of recurrences following radical surgery according to a nomogram reported by Kattan et al. Replication-defective adenovirus vector expressing REIC/Dkk-3 (Ad-REIC) was injected directly into the prostate (or metastatic lesion in patients who received prostatectomy) in escalating doses from 1.0×1010 to 1.0×1012 viral particle (vp). Each patient in category A received total of 2 times viral injections every 4 weeks. Patients in category B also received total of 2 times viral injections every 2 weeks, then received radical prostatectomy 6 weeks after second viral injection. Results: Three patients in category A, and 9 patients in category B were entered the present study. No significant side effects were observed. In category B, signs of immunological responses in surgically removed specimens (apoptosis induction of cancer cells in TUNEL staining and infiltration of CD8 positive cells (CTL) in immunohistochemical staining) were observed in second dose. These responses were remarkably observed in the third dose. Conclusions: This initial and preliminary report suggests the favorable safety profile and positive clinical responses in a clinical trial of Ad-REIC gene therapy for prostate cancer.