The University of Alabama at Birmingham (UAB) Comprehensive Cancer Center announced a new phase I clinical trial recently to investigate a genetically re-engineered herpes simplex virus as a treatment of malignant brain tumors. Standard treatment for these tumors ( such as glioblastoma, progressive malignant glioma, glioblastoma multiforme, anaplastic astroblastoma, and gliosarcoma) produces a 5-year survival rate of less than 5%. Surgery is not curative because the tumors generate microscopic fingers of tumor cells that invade the brain like a fine net.
Two Different Mutations
Researchers genetically altered the herpes simplex virus in two different mutations so as to prevent the virus from damaging normal brain cells while maintaining its destructive characteristics in malignant glioma cells. As part of the viral lifecycle, the herpes simplex virus enters tumor cells, alters its protein-making mechanisms to produce new virus cells, and in the process kills the host tumor cell. When the host cell dies, the new viral particles that are released attack nearby glioma cells but they do not damage nearby normal brain cellsproviding tumor specificity to the treatment. This self-generating aspect of the herpes simplex virus enables it to seek out and destroy the fine filaments of tumor that spread through the brain. In theory, as long as the virus cells find growing tumor cells, they will continue to replicate and kill them.
Added Safety Net
The genetically re-engineered herpes simplex virus, called G207, is also devised to be extremely sensitive to two common antiviral drugs, acyclovir and ganciclovir. That provides us with an extra margin of safety, says James Markert, MD, MPH, Cancer Center associate scientist and primary investigator for this study. We know that unmodified herpes simplex virus can produce encephalitis in humans. This engineered version can be easily treated with these two common drugs if immediate infection occurs. Also, we picked HSV because we know that about 90% of adults over the age of 30 already have some degree of immunity against the virus.
Adds Dr. Markert, The use of herpes simplex virus also has natural applications in the treatment of diseases, such as melanoma, breast cancer, colon cancer, and other adult and pediatric brain tumors.
This trial is sponsored by Neurovir pharmaceutical of Vancouver, Canada. For more information, consult Dr. Markert at (205) 975-6985.