PMID- 24434058 OWN - NLM STAT- MEDLINE DCOM- 20140428 LR - 20240213 IS - 1095-6859 (Electronic) IS - 0090-8258 (Print) IS - 0090-8258 (Linking) VI - 132 IP - 3 DP - 2014 Mar TI - Oncolytic vaccinia virotherapy for endometrial cancer. PG - 722-9 LID - S0090-8258(14)00020-1 [pii] LID - 10.1016/j.ygyno.2014.01.009 [doi] AB - OBJECTIVE: Oncolytic virotherapy is a promising modality in endometrial cancer (EC) therapy. In this study, we compared the efficacy of the Copenhagen and Wyeth strains of oncolytic vaccinia virus (VV) incorporating the human thyroidal sodium iodide symporter (hNIS) as a reporter gene (VVNIS-C and VVNIS-W) in EC. METHODS: Infectivity of VVNIS-C and VVNIS-W in type I (HEC1A, Ishikawa, KLE, RL95-2, and AN3 CA) and type II (ARK-1, ARK-2, and SPEC-2) human EC cell lines was evaluated. Athymic mice with ARK-2 or AN3 CA xenografts were treated with one intravenous dose of VVNIS-C or VVNIS-W. Tumor regression and in vivo infectivity were monitored via NIS expression using SPECT-CT imaging. RESULTS: All EC cell lines except KLE were susceptible to infection and killing by VVNIS-C and VVNIS-W in vitro. VVNIS-C had higher infectivity and oncolytic activity than VVNIS-W in all cell lines, most notably in AN3 CA. Intravenous VVNIS-C was more effective at controlling AN3 CA xenograft growth than VVNIS-W, while both VVNIS-C and VVNIS-W ceased tumor growth and induced tumor regression in 100% of mice bearing ARK-2 xenografts. CONCLUSION: Overall, VVNIS-C has more potent oncolytic viral activity than VVSIN-W in EC. VV appears to be most active in type II EC. Novel therapies are needed for the highly lethal type II EC histologies and further development of a VV clinical trial in type II EC is warranted. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Liu, Yu-Ping AU - Liu YP AD - Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Wang, Jiahu AU - Wang J AD - Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON KlY 4E9, Canada. FAU - Avanzato, Victoria A AU - Avanzato VA AD - Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA; Pennsylvania State University, State College, PA, USA. FAU - Bakkum-Gamez, Jamie N AU - Bakkum-Gamez JN AD - Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA. FAU - Russell, Stephen J AU - Russell SJ AD - Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN, USA. FAU - Bell, John C AU - Bell JC AD - Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON KlY 4E9, Canada. FAU - Peng, Kah-Whye AU - Peng KW AD - Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA. Electronic address: peng.kah@mayo.edu. LA - eng GR - R01 CA136547/CA/NCI NIH HHS/United States GR - R01CA136547/CA/NCI NIH HHS/United States GR - K12 HD065987/HD/NICHD NIH HHS/United States GR - P30CA015083/CA/NCI NIH HHS/United States GR - R01 CA129193/CA/NCI NIH HHS/United States GR - P30 CA015083/CA/NCI NIH HHS/United States GR - P50CA136393/CA/NCI NIH HHS/United States GR - R01CA129193/CA/NCI NIH HHS/United States GR - P50 CA136393/CA/NCI NIH HHS/United States GR - K12HD065987/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140114 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Symporters) RN - 4XE5NDT4K1 (sodium-iodide symporter) SB - IM MH - Animals MH - Endometrial Neoplasms/*therapy/*virology MH - Female MH - Genes, Reporter MH - Humans MH - Mice MH - Mice, Nude MH - Oncolytic Virotherapy/*methods MH - Symporters/genetics MH - Vaccinia virus/genetics/pathogenicity/*physiology MH - Xenograft Model Antitumor Assays PMC - PMC3977925 MID - NIHMS561301 OTO - NOTNLM OT - Copenhagen strain OT - Endometrial cancer OT - Vaccinia virus OT - Virotherapy OT - Wyeth strain COIS- Conflict of Interest Drs Russell, Wang, Bell and Peng, and Mayo Clinic have a financial interest in this research. EDAT- 2014/01/18 06:00 MHDA- 2014/04/29 06:00 PMCR- 2015/03/01 CRDT- 2014/01/18 06:00 PHST- 2013/12/11 00:00 [received] PHST- 2014/01/08 00:00 [revised] PHST- 2014/01/09 00:00 [accepted] PHST- 2014/01/18 06:00 [entrez] PHST- 2014/01/18 06:00 [pubmed] PHST- 2014/04/29 06:00 [medline] PHST- 2015/03/01 00:00 [pmc-release] AID - S0090-8258(14)00020-1 [pii] AID - 10.1016/j.ygyno.2014.01.009 [doi] PST - ppublish SO - Gynecol Oncol. 2014 Mar;132(3):722-9. doi: 10.1016/j.ygyno.2014.01.009. Epub 2014 Jan 14.