Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors

Yushui Wu, Xueqing Lun, Hongyuan Zhou, Limei Wang, Beichen Sun, John C. Bell, John W. Barrett, Douglas McFadden, Jaclyn A. Biegel, Donna L. Senger, Peter A. Forsyth

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Purpose: Rhabdoid tumors are highly aggressive pediatric tumors that are usually refractory to available treatments. The purpose of this study was to evaluate the therapeutic potential of two oncolytic viruses, myxoma virus (MV) and an attenuated vesicular stomatitis virus (VSVΔM51), in experimental models of human rhabdoid tumor. Experimental Design: Four human rhabdoid tumor cell lines were cultured in vitro and treated with live or inactivated control virus. Cytopathic effect, viral gene expression, infectious viral titers, and cell viability were examined at various time points after infection. To study viral oncolysis in vivo, human rhabdoid tumor cells were implanted s.c. in the hind flank or intracranially in CD-1 nude mice and treated with intratumoral (i.t.) or i.v. injections of live or UV-inactivated virus. Viral distribution and effects on tumor size and survival were assessed. Results: All rhabdoid tumor cell lines tested in vitro were susceptible to productive lethal infections by MV and VSVΔM51. I.t. injection of live MV or VSVΔM51 dramatically reduced the size of s.c. rhabdoid tumor xenografts compared with control animals. I.v. administration of VSVΔM51 or i.t. injection of MV prolonged the median survival of mice with brain xenografts compared with controls (VSVΔM51: 25 days versus 21 days, log-rank test, P = 0.0036; MV: median survival not reached versus 21 days, log-rank test, P = 0.0007). Most of the MV-treated animals (4 of 6; 66.7%) were alive and apparently "cured" when the experiment was arbitrarily ended (>180 days). Conclusions: These results suggest that VSVΔM51 and MV could be novel effective therapies against human rhabdoid tumor.

Original languageEnglish (US)
Pages (from-to)1218-1227
Number of pages10
JournalClinical Cancer Research
Volume14
Issue number4
DOIs
StatePublished - Feb 15 2008
Externally publishedYes

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Myxoma virus
Rhabdoid Tumor
Vesicular Stomatitis
Theoretical Models
Viruses
Tumor Cell Line
Heterografts
Injections
Oncolytic Viruses
Survival
Viral Genes
Infection
Nude Mice
Neoplasms
Cell Survival
Research Design
Therapeutics
Pediatrics
Gene Expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors. / Wu, Yushui; Lun, Xueqing; Zhou, Hongyuan; Wang, Limei; Sun, Beichen; Bell, John C.; Barrett, John W.; McFadden, Douglas; Biegel, Jaclyn A.; Senger, Donna L.; Forsyth, Peter A.

In: Clinical Cancer Research, Vol. 14, No. 4, 15.02.2008, p. 1218-1227.

Research output: Contribution to journalArticle

Wu, Y, Lun, X, Zhou, H, Wang, L, Sun, B, Bell, JC, Barrett, JW, McFadden, D, Biegel, JA, Senger, DL & Forsyth, PA 2008, 'Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors', Clinical Cancer Research, vol. 14, no. 4, pp. 1218-1227. https://doi.org/10.1158/1078-0432.CCR-07-1330
Wu, Yushui ; Lun, Xueqing ; Zhou, Hongyuan ; Wang, Limei ; Sun, Beichen ; Bell, John C. ; Barrett, John W. ; McFadden, Douglas ; Biegel, Jaclyn A. ; Senger, Donna L. ; Forsyth, Peter A. / Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 4. pp. 1218-1227.
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AU - Wu, Yushui

AU - Lun, Xueqing

AU - Zhou, Hongyuan

AU - Wang, Limei

AU - Sun, Beichen

AU - Bell, John C.

AU - Barrett, John W.

AU - McFadden, Douglas

AU - Biegel, Jaclyn A.

AU - Senger, Donna L.

AU - Forsyth, Peter A.

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N2 - Purpose: Rhabdoid tumors are highly aggressive pediatric tumors that are usually refractory to available treatments. The purpose of this study was to evaluate the therapeutic potential of two oncolytic viruses, myxoma virus (MV) and an attenuated vesicular stomatitis virus (VSVΔM51), in experimental models of human rhabdoid tumor. Experimental Design: Four human rhabdoid tumor cell lines were cultured in vitro and treated with live or inactivated control virus. Cytopathic effect, viral gene expression, infectious viral titers, and cell viability were examined at various time points after infection. To study viral oncolysis in vivo, human rhabdoid tumor cells were implanted s.c. in the hind flank or intracranially in CD-1 nude mice and treated with intratumoral (i.t.) or i.v. injections of live or UV-inactivated virus. Viral distribution and effects on tumor size and survival were assessed. Results: All rhabdoid tumor cell lines tested in vitro were susceptible to productive lethal infections by MV and VSVΔM51. I.t. injection of live MV or VSVΔM51 dramatically reduced the size of s.c. rhabdoid tumor xenografts compared with control animals. I.v. administration of VSVΔM51 or i.t. injection of MV prolonged the median survival of mice with brain xenografts compared with controls (VSVΔM51: 25 days versus 21 days, log-rank test, P = 0.0036; MV: median survival not reached versus 21 days, log-rank test, P = 0.0007). Most of the MV-treated animals (4 of 6; 66.7%) were alive and apparently "cured" when the experiment was arbitrarily ended (>180 days). Conclusions: These results suggest that VSVΔM51 and MV could be novel effective therapies against human rhabdoid tumor.

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