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 language | English (US) |
|---|---|
| Pages (from-to) | 9982-9990 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 65 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 2005 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
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 -