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Gynecol Oncol. 2014 Mar;132(3):722-9. doi: 10.1016/j.ygyno.2014.01.009. Epub 2014 Jan 14.

Oncolytic vaccinia virotherapy for endometrial cancer.

Author information

1
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
2
Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON KlY 4E9, Canada.
3
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA; Pennsylvania State University, State College, PA, USA.
4
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA.
5
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN, USA.
6
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.

Abstract

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.

KEYWORDS:

Copenhagen strain; Endometrial cancer; Vaccinia virus; Virotherapy; Wyeth strain

PMID:
24434058
PMCID:
PMC3977925
DOI:
10.1016/j.ygyno.2014.01.009
[Indexed for MEDLINE]
Free PMC Article

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