Adenovirus-mediated REIC/Dkk-3 Gene Therapy: Development of an Autologous Cancer Vaccination Therapy (Review)

Overview

Journal Oncol Lett

Specialty Oncology

Date 2014 Feb 15

PMID 24527065

Citations 20

Authors

Masami Watanabe

Yasutomo Nasu

Hiromi Kumon

Affiliations

Soon will be listed here.

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.

Citing Articles

The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.

Mourtada J, Thibaudeau C, Wasylyk B, Jung A Cells. 2024; 13(1).

PMID: 38201279 PMC: 10778571. DOI: 10.3390/cells13010075.

Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment.

Al Shareef Z, Ershaid M, Mudhafar R, Soliman S, Kypta R Cancers (Basel). 2022; 14(23).

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MiR-425 Promotes Migration and Invasion in Bladder Cancer by Targeting Dickkopf 3.

Ning J, Yu W, Cheng F, Rao T, Ruan Y J Cancer. 2020; 11(12):3424-3432.

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Recombinant adenovirus expressing a dendritic cell-targeted melanoma surface antigen for tumor-specific immunotherapy in melanoma mice model.

Guo L, Wang G, Li P, Wang C, Liu L Exp Ther Med. 2018; 15(6):5394-5402.

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Therapeutic effects of adenovirus-mediated CD and NIS expression combined with NaI/5-FC on human thyroid cancer.

Yuan M, Wei L, Zhou R, Xu H, Wang J, Bai Q Oncol Lett. 2018; 14(6):7431-7436.

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References

Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez R, Wang Y . Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010; 329(5993):849-53. PMC: 3732486. DOI: 10.1126/science.1188510. View

Tsuji T, Miyazaki M, Sakaguchi M, Inoue Y, Namba M . A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines. Biochem Biophys Res Commun. 2000; 268(1):20-4. DOI: 10.1006/bbrc.1999.2067. View

de Gruijl T, van den Eertwegh A, Pinedo H, Scheper R . Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunol Immunother. 2008; 57(10):1569-77. PMC: 2491427. DOI: 10.1007/s00262-008-0536-z. View

Yamada A, Sasada T, Noguchi M, Itoh K . Next-generation peptide vaccines for advanced cancer. Cancer Sci. 2012; 104(1):15-21. PMC: 7657262. DOI: 10.1111/cas.12050. View

Sakaguchi M, Huh N, Namba M . A novel tumor suppressor, REIC/Dkk-3 gene identified by our in vitro transformation model of normal human fibroblasts works as a potent therapeutic anti-tumor agent. Adv Exp Med Biol. 2011; 720:209-15. DOI: 10.1007/978-1-4614-0254-1_17. View

Onai T, Takai A, Setiamarga D, Holland L . Essential role of Dkk3 for head formation by inhibiting Wnt/β-catenin and Nodal/Vg1 signaling pathways in the basal chordate amphioxus. Evol Dev. 2012; 14(4):338-50. DOI: 10.1111/j.1525-142X.2012.00552.x. View

Schlom J . Therapeutic cancer vaccines: current status and moving forward. J Natl Cancer Inst. 2012; 104(8):599-613. PMC: 3328421. DOI: 10.1093/jnci/djs033. View

Mizobuchi Y, Matsuzaki K, Kuwayama K, Kitazato K, Mure H, Kageji T . REIC/Dkk-3 induces cell death in human malignant glioma. Neuro Oncol. 2008; 10(3):244-53. PMC: 2563047. DOI: 10.1215/15228517-2008-016. View

Kawasaki K, Watanabe M, Sakaguchi M, Ogasawara Y, Ochiai K, Nasu Y . REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer. Cancer Gene Ther. 2008; 16(1):65-72. DOI: 10.1038/cgt.2008.58. View

10.

Romero D, Kawano Y, Bengoa N, Walker M, Maltry N, Niehrs C . Downregulation of Dickkopf-3 disrupts prostate acinar morphogenesis through TGF-β/Smad signalling. J Cell Sci. 2013; 126(Pt 8):1858-67. DOI: 10.1242/jcs.119388. View

11.

Watanabe M, Kashiwakura Y, Huang P, Ochiai K, Futami J, Li S . Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. Int J Oncol. 2009; 34(3):657-63. DOI: 10.3892/ijo_00000191. View

12.

Than S, Kataoka K, Sakaguchi M, Murata H, Abarzua F, Taketa C . Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma. Oncol Rep. 2011; 25(4):989-95. DOI: 10.3892/or.2011.1149. View

13.

Veeck J, Dahl E . Targeting the Wnt pathway in cancer: the emerging role of Dickkopf-3. Biochim Biophys Acta. 2011; 1825(1):18-28. DOI: 10.1016/j.bbcan.2011.09.003. View

14.

Nakamura R, Hackam A . Analysis of Dickkopf3 interactions with Wnt signaling receptors. Growth Factors. 2010; 28(4):232-42. PMC: 2950226. DOI: 10.3109/08977191003738832. View

15.

Sato H, Suzuki H, Toyota M, Nojima M, Maruyama R, Sasaki S . Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors. Carcinogenesis. 2007; 28(12):2459-66. DOI: 10.1093/carcin/bgm178. View

16.

Naume B, Espevik T . Effects of IL-7 and IL-2 on highly enriched CD56+ natural killer cells. A comparative study. J Immunol. 1991; 147(7):2208-14. View

17.

Kobayashi K, Ouchida M, Tsuji T, Hanafusa H, Miyazaki M, Namba M . Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells. Gene. 2002; 282(1-2):151-8. DOI: 10.1016/s0378-1119(01)00838-1. View

18.

Niwa H, Yamamura K, Miyazaki J . Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene. 1991; 108(2):193-9. DOI: 10.1016/0378-1119(91)90434-d. View

19.

Tanimoto R, Abarzua F, Sakaguchi M, Takaishi M, Nasu Y, Kumon H . REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer. Int J Mol Med. 2007; 19(3):363-8. View

20.

Zhang K, Watanabe M, Kashiwakura Y, Li S, Edamura K, Huang P . Expression pattern of REIC/Dkk-3 in various cell types and the implications of the soluble form in prostatic acinar development. Int J Oncol. 2010; 37(6):1495-501. DOI: 10.3892/ijo_00000802. View