title: Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review).
abstract: Reduced expression in immortalized cells (REIC)/Dickkopf (Dkk)-3 is a tumor suppressor and therapeutic gene and has been studied with respect to the application of cancer gene therapy. Our previous studies demonstrated that the intratumoral injection of an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC) suppresses tumor growth in mouse models of prostate, breast and testicular cancer and malignant mesothelioma. The mechanisms underlying these antitumor therapeutic effects have only been clarified recently. It has been demonstrated that Ad-REIC treatment inhibits cancer progression via the upregulation of systemic anticancer immunity. Under experimental conditions, autologous cancer vaccination via cancer-specific apoptosis and anticancer immune activation is a possible therapeutic mechanism. The robust anticancer effects observed in previous preclinical studies support the clinical utility of Ad-REIC. At present, a phase I-IIa study of Ad-REIC gene therapy in prostate cancer patients is ongoing. The current study reviews the observations of previous fundamental studies and summarizes the anticancer mechanisms of intratumoral Ad-REIC treatment in terms of cancer vaccination.
authors: Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Okayama 700-8558, Japan ; Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan.
authors: Masami
authors: M
authors: Watanabe
authors: Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Okayama 700-8558, Japan ; Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan.
authors: Yasutomo
authors: Y
authors: Nasu
authors: Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan.
authors: Hiromi
authors: H
authors: Kumon
keywords: REIC/Dkk-3; apoptosis; cancer vaccine; dendritic cells; gene therapy