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.c.) 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 UVinactivated 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. (Cancer Res 2005; 65(21): 9982-90)

Bovine herpesvirus type 1 as a novel oncolytic virus

“…20 Myxoma virus, a rabbit poxvirus with a similar restricted tropism, functions as an oncolytic virus in human tumor cells bearing deficiencies in type I IFN and tumor necrosis factor-a (TNFa) pathways. 23,24 Before investigating the oncolytic capacity of BHV-1, we first confirmed the restriction of normal human cells against BHV-1 replication and CPE induction. A panel of six non-immortalized, non-transformed cell types (refer to Table 1 for cell type information) were infected with increasing amounts of BHV-1, and CPE was monitored 3 days post-infection.…”

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host

“…A recent report has indicated that this virus exhibits a natural tropism for many human tumor cells [93], indicating that this virus could be used as a therapy in cancer treatment. Studies in a mouse model of glioma has shown that this virus is quite effective in infecting tumor tissue in vivo and effectively 'cured' mice from these brain tumors [56]. These studies have fostered enthusiasm in the prospect of using this virus clinically to treat human cancers [66].…”

Comparative evaluation of survivin, midkine, and CXCR4 promoters for transcriptional targeting of glioma gene therapy

“…In gene therapy approaches, a therapeutic gene for mutation compensation, immunopotentiation, or prodrug activation is transferred. [2][3][4][5][6][7] In virotherapy, tumor cell killing is achieved by oncolysis; that is, virus replication induced cell killing. [8][9][10] Both of these therapeutic interventions allow for specific antitumor effects via molecular targeting strategies that exploit tumor markers.…”