Cancer-killing viruses

Among the viruses currently being studied as oncolytic agents is herpes simplex virus 1 (HSV-1). Genetically modified HSV-1 (34.5) infects and destroys neuronal cancer cells while leaving normal neurons unharmed. It was created by deleting a virally encoded gene, 34.5, required for neurovirulence. Unfortunately, the 34.5 virus is deficient for viral replication in tumor cells, allowing surviving cancer cells to reestablish the tumor after treatment with the modified virus.

Ian Mohr’s laboratory at the New York University School of Medicine has addressed this problem by identifying a mutant form of the 34.5 virus, which was isolated for its increased replication properties following the passage of the original virus through neuronal carcinoma cells (EMBO J. 1996, 15, 4759–4766). This suppressor virus bypasses a block in protein synthesis, resulting in increased viral replication in tumor cells.

Mohr and colleagues (Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 8804–8808) have now characterized the ability of the virus to replicate and its oncolytic activity.Their findings show that the suppressor virus displays between 10²- and 10⁴-fold more viral replication than the parental 34.5 virus in prostate and glioblastoma tumor cell lines. Additionally, in nude mice implanted with tumors from human prostate cancer cells, the scientists showed that, at three different dosage levels, the suppressor virus is more effective than the 34.5 virus in reducing the size and growth rate of the implanted tumors. Furthermore, only mice treated with the suppressor virus showed a complete regression of the tumor. Finally, immunohistochemistry illustrated the localization of the suppressor virus to the prostate carcinoma cells, signifying tumor-specific virulence.

These data indicate the use of genetic selection for producing tumor-targeted viruses as a realistic tool for creating safe and effective weapons against cancer.