A Pox on Your Brain Tumor

In 1796, Edward Jenner was the first to discover that inoculation of cowpox viruses was safe in humans and protected against smallpox. His work ultimately led to the worldwide eradiation of smallpox, one of the greatest medical achievements in the 20th century. The virus in the vaccine, termed vaccinia, which has been given to hundreds of millions of people, may help mankind once again.

Jennerex Biotherapeutics, named after Jenner and based in San Francisco, is conducting clinical trials of a vaccinia virus variant called JX-594 that is genetically engineered to infect cancer cells and to help alert the immune system to the cancer. Published results in patients with liver cancers appear promising.

In an article published in the November issue of Molecular Therapy, Lun, et al. now report that JX-594 might also be useful for the most common and deadliest of brain cancers, malignant glioma, for which there are no curative treatments available. The researchers found that JX-594 killed malignant glioma cells in culture, and when injected into brain tumors in mice and rats the virus prolonged animal survival. The effect was even more dramatic when they also gave animals a commonly used drug known to slow growth of some cancer cells and decrease immunity (rapamycin), even curing some of the rats.

One theory about how tumors return after shrinking from traditional therapy is by harboring resistant cells that regenerate the cancer, variably termed cancer stem cells, tumor initiating cells, or tumor promoting cells. It is thought that for any therapy to be curative it needs to kill these cells in addition to the bulk of tumor cells. JX-594 was able to infect and kill these cells as well, and did so better than several other viruses tested. JX-594 did cause brain inflammation when injected into normal brains at high doses, so much work still needs to be done in animals to determine how to use it in the safest way in clinical trials. Despite this concern, given the lack of options for patients with malignant gliomas, this article gives us some hope for future success.