Scientists from Duke-NUS Medical School (Duke-NUS) have developed a new approach using the Zika virus to destroy brain cancer cells and inhibit tumor growth, while sparing healthy cells. Using Zika virus vaccine candidates developed at Duke-NUS, the team discovered how these strains target rapidly proliferating cells over mature cells—making them an ideal option to target fast-growing cancerous cells in the adult brain.
Their findings, published in the Journal of Translational Medicine, potentially offer a new treatment alternative for brain cancer patients who currently have a poor prognosis.
Glioblastoma multiforme is the most common malignant brain cancer, with more than 300,000 patients diagnosed annually worldwide. Survival rates for such patients are poor (around 15 months), mainly due to high incidence of tumor recurrence and limited treatment options. For such patients, oncolytic virotherapy—or the use of engineered viruses to infect and kill cancer cells—may address the current therapeutic challenges.
Zika virus is one such option in early development. The Duke-NUS team used Zika virus live-attenuated vaccine (ZIKV-LAV) strains, which are “weakened” viruses with limited ability to infect healthy cells but can still grow rapidly and spread within a tumor mass.
“We selected Zika virus because it naturally infects rapidly multiplying cells in the brain, allowing us to reach cancer cells that are traditionally difficult to target. Our ZIKV-LAV strains also replicate themselves in brain cancer cells, making this a living therapy that can spread and attack neighboring diseased cells,” said Dr. Carla Bianca Luena Victorio, first author of the paper and Senior Research Fellow at the Cancer & Stem Cell Biology Research Program at Duke-NUS.
Dr. Victorio and the team determined that ZIKV-LAV strains were highly effective in infecting cancer cells as these viruses bind to proteins that are present in high levels only in cancer cells and not in healthy cells. Upon infecting a cancer cell, these virus strains hijack the cell's resources to reproduce, ultimately killing the cell.
As the cancer cell's protective membrane ruptures upon death, it releases its contents, including virus progeny that can infect and kill neighboring cancer cells. In addition, some cellular proteins released from the infected cells can activate an immune response to further inhibit tumor growth.
Through their experiments, the team observed that infection from ZIKV-LAV strains caused 65% to 90% of glioblastoma multiforme tumor cells to die. While the ZIKV-LAV strains also infected 9% to 20% of cells from blood vessels in the brain, the infection did not kill these healthy cells. In contrast, the original parent Zika virus strain killed up to 50% of healthy brain cells.
The scientists also discovered that the ZIKV-LAV strains were not able to reproduce well even when they managed to infect healthy cells. The amount of virus measured in healthy brain cells infected with ZIKV-LAV was only 0.36 to 9 times higher than before infection. In contrast, the amount of virus in brain cancer cells infected with ZIKV-LAV was 100 to a billion times higher than before infection. This further illustrates that conditions in cancer cells are significantly more conducive for virus reproduction than in normal cells.
Source: Duke-NUS Medical School