Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo

Marianne M. Stanford, Mae Shaban, John W. Barrett, Steven J. Werden, Philippe Alexandre Gilbert, Joe Bondy-Denomy, Lisa MacKenzie, Kevin C. Graham, Ann F. Chambers, Douglas McFadden

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Myxoma virus (MV) is a rabbit-specific poxvirus, whose unexpected tropism to human cancer cells has led to studies exploring its potential use in oncolytic therapy. MV infects a wide range of human cancer cells in vitro, in a manner intricately linked to the cellular activation of Akt kinase. MV has also been successfully used for treating human glioma xenografts in immunodeficient mice. This study examines the effectiveness of MV in treating primary and metastatic mouse tumors in immunocompetent C57BL6 mice. We have found that several mouse tumor cell lines, including B16 melanomas, are permissive to MV infection. B16F10 cells were used for assessing MV replication and efficacy in syngeneic primary tumor and metastatic models in vivo. Multiple intratumoral injections of MV resulted in dramatic inhibition of tumor growth. Systemic administration of MV in a lung metastasis model with B16F10LacZ cells was dramatically effective in reducing lung tumor burden. Combination therapy of MV with rapamycin reduced both size and number of lung metastases, and also reduced the induced antiviral neutralizing antibody titres, but did not affect tumor tropism. These results show MV to be a promising virotherapeutic agent in immunocompetent animal tumor models, with good efficacy in combination with rapamycin.

Original languageEnglish (US)
Pages (from-to)52-59
Number of pages8
JournalMolecular Therapy
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Myxoma virus
Neoplasms
Tropism
Sirolimus
Lung
Neoplasm Metastasis
Poxviridae
Experimental Melanomas
Virus Diseases
Virus Replication
Neutralizing Antibodies
Tumor Burden
Tumor Cell Line
Heterografts
Glioma
Antiviral Agents

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Stanford, M. M., Shaban, M., Barrett, J. W., Werden, S. J., Gilbert, P. A., Bondy-Denomy, J., ... McFadden, D. (2008). Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. Molecular Therapy, 16(1), 52-59. https://doi.org/10.1038/sj.mt.6300348

Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. / Stanford, Marianne M.; Shaban, Mae; Barrett, John W.; Werden, Steven J.; Gilbert, Philippe Alexandre; Bondy-Denomy, Joe; MacKenzie, Lisa; Graham, Kevin C.; Chambers, Ann F.; McFadden, Douglas.

In: Molecular Therapy, Vol. 16, No. 1, 01.01.2008, p. 52-59.

Research output: Contribution to journalArticle

Stanford, MM, Shaban, M, Barrett, JW, Werden, SJ, Gilbert, PA, Bondy-Denomy, J, MacKenzie, L, Graham, KC, Chambers, AF & McFadden, D 2008, 'Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo', Molecular Therapy, vol. 16, no. 1, pp. 52-59. https://doi.org/10.1038/sj.mt.6300348
Stanford MM, Shaban M, Barrett JW, Werden SJ, Gilbert PA, Bondy-Denomy J et al. Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. Molecular Therapy. 2008 Jan 1;16(1):52-59. https://doi.org/10.1038/sj.mt.6300348
Stanford, Marianne M. ; Shaban, Mae ; Barrett, John W. ; Werden, Steven J. ; Gilbert, Philippe Alexandre ; Bondy-Denomy, Joe ; MacKenzie, Lisa ; Graham, Kevin C. ; Chambers, Ann F. ; McFadden, Douglas. / Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo. In: Molecular Therapy. 2008 ; Vol. 16, No. 1. pp. 52-59.
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