Oncolytic vaccinia virotherapy for endometrial cancer

被引：18

作者：

Liu, Yu-Ping ^{[1
]}

Wang, Jiahu ^{[4
]}

Avanzato, Victoria A. ^{[1
,5
]}

Bakkum-Gamez, Jamie N. ^{[3
]}

Russell, Stephen J. ^{[1
,2
]}

Bell, John C. ^{[4
]}

Peng, Kah-Whye ^{[1
,3
]}

机构：

[1] Mayo Clin, Dept Mol Med, 200 First St SW, Rochester, MN 55905 USA

[2] Mayo Clin, Div Hematol, Rochester, MN 55905 USA

[3] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN 55905 USA

[4] Ottawa Hosp, Res Inst, Ctr Innovat Canc Res, Ottawa, ON K1Y 4E9, Canada

[5] Penn State Univ, State Coll, PA USA

来源：

GYNECOLOGIC ONCOLOGY | 2014年 / 132卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Endometrial cancer; Virotherapy; Vaccinia virus; Copenhagen strain; Wyeth strain; PHASE-II TRIAL; THYMIDINE KINASE; PROSTATE-CANCER; VIRUS; RECURRENT; THERAPY; CARCINOMA; PERSISTENT; POXVIRUS; RADIOTHERAPY;

D O I：

10.1016/j.ygyno.2014.01.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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! (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. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：722 / 729

页数：8

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