The result is an engineered herpes virus that has prolonged survival in laboratory mice with brain tumors, and even cured some, offering promise as a potential new treatment for difficult-to-treat brain tumors.
Dr. James M. Markert described his team`s novel approach to Reuters Health. "We sought to increase the efficacy of genetically-engineered (herpes simplex virus-1) by adding the gene for interleukin-12 (IL-12), an activator of the immune system, to the virus` (own) DNA," he explained.
Herpes simplex virus-1 (HSV-1) is a common infectious agent probably best known for its association with fever blisters.
A genetically-modified herpes simplex virus has already been used experimentally on brain tumors, Markert noted, but "unfortunately, the virus does not uniformly eradicate all tumor cells."
In their current study using mice, Markert and colleagues "found that even in (animals) with tumors that were relatively resistant to treatment with the HSV-1... alone, we could produce long-term increases in survival (using the virus plus gene strategy)... with some mice apparently cured of their tumors"
Concerns that the treatment might result in damage to delicate tissues of the nervous system were unfounded, even when high doses were used, the researchers report in the February 29th issue of the Proceedings of the National Academy of Sciences.
Markert attributes the apparent success of the treatment to a combination of direct destruction of the tumor by the virus and an immune response triggered by IL-12.
Malignant brain tumors are often difficult to treat. Markert and his team cite the example of the "grim prognosis" attached to the diagnosis of glioblastoma. Most patients survive only about 1 year after diagnosis, even with treatment.
Though statistics such as these lend some urgency to the development of effective therapeutic options, Markert emphasized that additional testing is essential before studies in humans can even be considered. Consequently, his team will be conducting "further preclinical studies of the virus to see if it will be safe for clinical trials."
SOURCE: Proceedings of the National Academy of Sciences 2000;97:2208-2213.