Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas

Xueqing Lun, Wenqing Yang, Tommy Alain, Zhong Qiao Shi, Huong Muzik, John W. Barrett, Douglas McFadden, John Bell, Mark G. Hamilton, Donna L. Senger, Peter A. Forsyth

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.e.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251; P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma virus-treated animals (12 of 13, 92%) were alive and apparently "cured" when the experiment was finished (>130 days). Interestingly, we found a selective and long-lived myxoma virus infection in gliomas in vivo. This is the first demonstration of the oncolytic activity of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of the rabbit host, its capacity to be genetically modified, its ability to produce a long-lived infection in human tumor cells, and the lack of preexisting antibodies in the human population suggest that myxoma virus may be an attractive oncolytic agent against human malignant glioma.

Original languageEnglish (US)
Pages (from-to)9982-9990
Number of pages9
JournalCancer Research
Volume65
Issue number21
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Fingerprint

Myxoma virus
Oncolytic Viruses
Glioma
Rabbits
Poxviridae
Survival
Virus Diseases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lun, X., Yang, W., Alain, T., Shi, Z. Q., Muzik, H., Barrett, J. W., ... Forsyth, P. A. (2005). Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. Cancer Research, 65(21), 9982-9990. https://doi.org/10.1158/0008-5472.CAN-05-1201

Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. / Lun, Xueqing; Yang, Wenqing; Alain, Tommy; Shi, Zhong Qiao; Muzik, Huong; Barrett, John W.; McFadden, Douglas; Bell, John; Hamilton, Mark G.; Senger, Donna L.; Forsyth, Peter A.

In: Cancer Research, Vol. 65, No. 21, 01.11.2005, p. 9982-9990.

Research output: Contribution to journalArticle

Lun, X, Yang, W, Alain, T, Shi, ZQ, Muzik, H, Barrett, JW, McFadden, D, Bell, J, Hamilton, MG, Senger, DL & Forsyth, PA 2005, 'Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas', Cancer Research, vol. 65, no. 21, pp. 9982-9990. https://doi.org/10.1158/0008-5472.CAN-05-1201
Lun, Xueqing ; Yang, Wenqing ; Alain, Tommy ; Shi, Zhong Qiao ; Muzik, Huong ; Barrett, John W. ; McFadden, Douglas ; Bell, John ; Hamilton, Mark G. ; Senger, Donna L. ; Forsyth, Peter A. / Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. In: Cancer Research. 2005 ; Vol. 65, No. 21. pp. 9982-9990.
@article{659aa637050f4a50a922aa2d1ccfb41c,
title = "Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas",
abstract = "Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5{\%}) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.e.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251; P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma virus-treated animals (12 of 13, 92{\%}) were alive and apparently {"}cured{"} when the experiment was finished (>130 days). Interestingly, we found a selective and long-lived myxoma virus infection in gliomas in vivo. This is the first demonstration of the oncolytic activity of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of the rabbit host, its capacity to be genetically modified, its ability to produce a long-lived infection in human tumor cells, and the lack of preexisting antibodies in the human population suggest that myxoma virus may be an attractive oncolytic agent against human malignant glioma.",
author = "Xueqing Lun and Wenqing Yang and Tommy Alain and Shi, {Zhong Qiao} and Huong Muzik and Barrett, {John W.} and Douglas McFadden and John Bell and Hamilton, {Mark G.} and Senger, {Donna L.} and Forsyth, {Peter A.}",
year = "2005",
month = "11",
day = "1",
doi = "10.1158/0008-5472.CAN-05-1201",
language = "English (US)",
volume = "65",
pages = "9982--9990",
journal = "Cancer Research",
issn = "0008-5472",
number = "21",

}

TY - JOUR

T1 - Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas

AU - Lun, Xueqing

AU - Yang, Wenqing

AU - Alain, Tommy

AU - Shi, Zhong Qiao

AU - Muzik, Huong

AU - Barrett, John W.

AU - McFadden, Douglas

AU - Bell, John

AU - Hamilton, Mark G.

AU - Senger, Donna L.

AU - Forsyth, Peter A.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.e.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251; P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma virus-treated animals (12 of 13, 92%) were alive and apparently "cured" when the experiment was finished (>130 days). Interestingly, we found a selective and long-lived myxoma virus infection in gliomas in vivo. This is the first demonstration of the oncolytic activity of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of the rabbit host, its capacity to be genetically modified, its ability to produce a long-lived infection in human tumor cells, and the lack of preexisting antibodies in the human population suggest that myxoma virus may be an attractive oncolytic agent against human malignant glioma.

AB - Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.e.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251; P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma virus-treated animals (12 of 13, 92%) were alive and apparently "cured" when the experiment was finished (>130 days). Interestingly, we found a selective and long-lived myxoma virus infection in gliomas in vivo. This is the first demonstration of the oncolytic activity of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of the rabbit host, its capacity to be genetically modified, its ability to produce a long-lived infection in human tumor cells, and the lack of preexisting antibodies in the human population suggest that myxoma virus may be an attractive oncolytic agent against human malignant glioma.

UR - http://www.scopus.com/inward/record.url?scp=27544508998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27544508998&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-05-1201

DO - 10.1158/0008-5472.CAN-05-1201

M3 - Article

VL - 65

SP - 9982

EP - 9990

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 21

ER -