Putting a Pox on Cancer

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Science  02 Nov 2007:
Vol. 318, Issue 5851, pp. 717
DOI: 10.1126/science.318.5851.717b

Advances in gene therapy and other technologies have helped revive the idea that viruses can be harnessed to destroy tumor cells. Over a dozen distinct families of viruses are being engineered to optimize their “oncolytic” potential— i.e., their ability to replicate in and kill tumor cells without harming normal tissue. Among these is vaccinia virus, whose desirable features as an oncolytic agent include the ability to spread rapidly through the blood to epidermal tissues and a well-established safety profile in humans because of its use as a vaccine for smallpox.

Two recent studies highlight the diverse ways in which vaccinia virus is being redesigned for use as a cancer therapy. Thorne et al. generated a strain of vaccinia that (i) specifically targets tumor cells with activation of transcription factor E2F and the epidermal growth factor receptor signaling pathway, and (ii) produces in the tumor vicinity a host-encoded cytokine (GM-CSF) that appears to enhance the body's antitumor immune response. In independent work, Zhang et al. inserted into the vaccinia genome transgenes encoding three different light-emitting proteins, a strategy that allowed the antitumor activity of the virus to be monitored in real time by optical imaging. Both virus strains induced regression of tumors in preclinical models and, importantly, therapeutic activity was seen when the viruses were administered systemically, the delivery method most relevant for clinical therapies targeting solid tumors.— PAK

J. Clin. Invest.117 10.1172/JC132727 (2007);

Cancer Res. 67 10038 (2007).

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