Virus May Battle Brain Tumors Better With Bacterial Enzymes
OSUCCC – James researchers have shown that oncolytic viruses, which are engineered to destroy cancer cells, might be more effective against brain malignancies if equipped with an enzyme that helps them penetrate the tumor.
The enzyme, called chondroitinase, helps the virus work its way through thickets of protein molecules that fill spaces between cells. When tested in animals transplanted with a human glioblastoma, the most common and deadly form of brain cancer, the enzyme-armed virus improved survival by 52 percent compared with controls, and in some cases it eliminated the tumor.
“Our results show for the first time that an oncolytic virus with this enzyme can spread more effectively through the tumor, underscoring the potential for using chondroitinases to enhance the capacity of oncolytic viruses to destroy cancer cells,” says study leader Balveen Kaur, PhD, of the OSUCCC – James’ Viral Oncology Program.
Derived from the intestinal bacterium Proteus vulgaris, the enzyme removes sugar chains that branch from proteoglycans that fill the “narrow spaces between cells. Cutting away these branches helps the virus spread through the tumor.
In this study, Kaur and collaborators injected human glioblastoma cells under the skin of eight mice. They treated the resulting tumors with the enzyme-armed virus. These mice survived an average of 28 days, with two animals remaining tumor-free after 80 days. Control animals, treated with a virus that lacked the enzyme, survived an average of 16 days.
In another experiment, mice with human glioblastomas transplanted into the brain survived 32 days versus 21 days for control animals, an improvement of 52 percent. Again, two animals lived more than 80 days and showed no trace of the tumor afterward.
Published in the journal Clinical Cancer Research.