Myxoma virus oncolysis of primary and metastatic B16F10 mouse tumors in vivo.
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.
Stanford
Marianne M
MM
BioTherapeutics Research Group, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Shaban
Mae
M
Barrett
John W
JW
Werden
Steven J
SJ
Gilbert
Philippe-Alexandre
PA
Bondy-Denomy
Joe
J
Mackenzie
Lisa
L
Graham
Kevin C
KC
Chambers
Ann F
AF
McFadden
Grant
G
D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000628:therapy* / Q000821:virology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000628:therapy* / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009233:Myxoma virus / Q000187:drug effects / Q000235:genetics; D050130:Oncolytic Virotherapy / Q000379:methods; D011817:Rabbits; D020123:Sirolimus / Q000627:therapeutic use
D000277:Adjuvants, Pharmaceutic; D000903:Antibiotics, Antineoplastic; D020123:Sirolimus