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

doi:10.1016/j.ygyno.2014.01.009

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 journal › Article › peer-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 language	English (US)
Pages (from-to)	722-729
Number of pages	8
Journal	Gynecologic oncology
Volume	132
Issue number	3
DOIs	https://doi.org/10.1016/j.ygyno.2014.01.009
State	Published - Mar 2014

Keywords

Copenhagen strain
Endometrial cancer
Vaccinia virus
Virotherapy
Wyeth strain

ASJC Scopus subject areas

Oncology
Obstetrics and Gynecology

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10.1016/j.ygyno.2014.01.009

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@article{f2a7e979d7c44c278c2eaaf4acf1263d,

title = "Oncolytic vaccinia virotherapy for endometrial cancer",

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",

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

note = "Funding Information: This work was supported by Mayo Clinic Comprehensive Cancer Center ( P30CA015083 ), and grants from the National Institutes of Health National Cancer Institute ( R01CA129193 , R01CA136547 ), Mayo Clinic Ovarian SPORE ( P50CA136393 ), Office of Women's Health Research Building Interdisciplinary Careers in Women's Health ( K12 HD065987 ) and a generous gift from Harry and Lorraine Hammerly. ",

year = "2014",

month = mar,

doi = "10.1016/j.ygyno.2014.01.009",

language = "English (US)",

volume = "132",

pages = "722--729",

journal = "Gynecologic oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

number = "3",

}

TY - JOUR

T1 - Oncolytic vaccinia virotherapy for endometrial cancer

AU - Liu, Yu Ping

AU - Wang, Jiahu

AU - Avanzato, Victoria A.

AU - Bakkum-Gamez, Jamie N.

AU - Russell, Stephen J.

AU - Bell, John C.

AU - Peng, Kah Whye

N1 - Funding Information: This work was supported by Mayo Clinic Comprehensive Cancer Center ( P30CA015083 ), and grants from the National Institutes of Health National Cancer Institute ( R01CA129193 , R01CA136547 ), Mayo Clinic Ovarian SPORE ( P50CA136393 ), Office of Women's Health Research Building Interdisciplinary Careers in Women's Health ( K12 HD065987 ) and a generous gift from Harry and Lorraine Hammerly.

PY - 2014/3

Y1 - 2014/3

N2 - 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.

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.

KW - Copenhagen strain

KW - Endometrial cancer

KW - Vaccinia virus

KW - Virotherapy

KW - Wyeth strain

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M3 - Article

C2 - 24434058

AN - SCOPUS:84896400186

SN - 0090-8258

VL - 132

SP - 722

EP - 729

JO - Gynecologic oncology

JF - Gynecologic oncology

IS - 3

ER -

Oncolytic vaccinia virotherapy for endometrial cancer

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