Oncolytic vaccinia virotherapy for endometrial cancer

Yu Ping Liu, Jiahu Wang, Victoria A. Avanzato, Jamie N. Bakkum-Gamez, Stephen J. Russell, John C. Bell, Kah Whye Peng

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)722-729
Number of pages8
JournalGynecologic oncology
Volume132
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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