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Reprogrammed Herpes Virus Blocks Neuroblastoma Stem Cells

The results of a study led by Cincinnati Children's Hospital Medical Center—in which researchers identified possible cancer stem cells for neuroblastoma in mice and then used a reprogrammed herpes virus to block tumor formation by targeting and killing the cells—add to a collection of data showing that early-stage cancer precursor cells that have stem cell-like properties may explain how some types of cancer develop, become treatment resistant, and are prone to relapse.

“The main finding of our study is that pediatric neuroblastomas seem to have a population of cells with stem-cell characteristics that we may need to target for therapy," said Timothy Cripe, MD, PhD, senior investigator and a physician/researcher, division of Hematology/Oncology. “We also show that one promising approach for targeted treatment is biological therapy, such as an engineered oncolytic virus that seeks out and kills progenitor cells that could be the seeds of cancers.”

The researchers came to these findings by growing human neuroblastoma cells in laboratory cultures that contained cells that exhibited biological properties of neural stem cells, which then generated cell colonies that divided, grew, and were capable of diverse differentiation like stem cells. These cells carried such proteins as CD133 and nestin, known biological markers for nerve stem cells, and advanced into tumor-like cells that were tumorigenic.

These tumorigenic cells—infected with the oncolytic herpes simplex virus rQNestin34.5, which carries a molecular promoter for nestin that “causes it to seek out the protein and cancerous, or precancerous, cells where nestin resides”—were injected into mice to see if neuroblastoma tumors would form. After 60 days of observation, the researchers reported that rQNestin34 “abolished tumor growth” by attacking apparent tumor-initiating cells, as no tumors formed in any of the mice.

When using cells infected with the oncolytic herpes virus called rQLuc, which doesn’t target cells containing the nestin protein, all treated mice formed tumors within 40 days.

"Targeting and hitting the cells after they are already in the mice will be another matter," said Cripe, cautioning that much more research is needed before determining if rQNestin34.5 could be used in the treatment of human patients with neuroblastoma.

For more on this story, check out the press release from Cincinnati Children's Hospital Medical Center.

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