Editors' ChoiceOncolytic Viruses

Measles Versus Melanoma

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Science Translational Medicine  11 Jan 2012:
Vol. 4, Issue 116, pp. 116ec7
DOI: 10.1126/scitranslmed.3003670

Measles and melanoma are both best avoided; but measles—a viral disease that used to cause ~2.6 million deaths each year—is now successfully controlled with a vaccine. Unfortunately, the deadly skin cancer melanoma has yet to be thwarted. Now, in a Spy vs. Spy* twist, Donnelly and colleagues turn the vaccine strain of the measles virus (MV) into an oncolytic hammer that targets melanoma.

The authors used the Edmonston single-stranded, enveloped RNA vaccine strain of MV as their therapeutic agent. Specifically, in four human melanoma cell lines, Donnelly et al. used a live-dead assay and characteristic cytopathology to show that MV infection directly induced melanoma cell–specific cytotoxicity in a dose- and time-dependent manner. But direct delivery of the death sentence was not the only trick MV had up its sleeve. In a second set of experiments, the authors showed that MV infection of melanoma cells stimulated the release of inflammatory cytokines. When melanoma cells were infected with MV, all four cell lines secreted interleukin (IL)–6, IL-8, and various interferons in a dose-dependent fashion, as measured by enzyme-linked immunosorbent assays (ELISAs) performed with cell-free culture supernatants 48 hours after infection. To confirm that primary melanoma cells were susceptible to MV oncolysis, metastatic deposits from three patients with proven melanoma were cultured and exposed to MV; live-dead assays confirmed cytotoxicity, and ELISA confirmed cytokine release.

To study viral-mediated antitumor immunity, human peripheral blood mononuclear cells (PBMCs) were collected from donors and treated overnight with MV. The PBMCs were then assayed with chromium-labeled tumor targets, and the chromium-release assay displayed enhanced killing of tumor cells. Natural killer immune cells were shown to be responsible for MV-induced innate immune activation. Finally, the authors showed that MV stimulated antitumor immunity by activating antigen-presenting dendritic cells and cytotoxic T cells that were both directed specifically against melanoma cells.

Sneaky and aggressive, melanoma is a deadly cancer. Donnelly et al. have introduced a clever anticancer approach that exploits the multifunctional effects of a viral adversary. Future hurdles include in vivo evaluation of this strategy, but in the ongoing game of spy versus spy, MV may be an effective weapon.

*A comic strip from Mad magazine in which two spies try to outwit each other.

O. G. Donnelly et al., Measles virus causes immunogenic cell death in human melanoma. Gene Ther. 15 December 2011(10.1038/gt.2011.205). [PubMed]

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