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Herpes and Brain Tumors: Or What happens in Vegas?

tumor

Herpes, it isn’t just a pest that follows you home from Vegas, not anymore anyway. New research has found a [not so] new use for the virus. Harvard Stem Cell Institute [HSCI] scientists at Massachusetts General Hospital have repurposed the herpes virus to help fight brain tumors. 

The investigators reported that by trapping virus-loaded stem cells in a gel and applying them to tumors they significantly improved survival in mice with glioblastoma multiforme, which is not only the most common brain tumor in human adults, it also happens to be the most difficult to treat.

The idea isn’t a new one, not by a long shot. However, the past clinical trials had limited success in treating tumors. The problem those researchers couldn’t overcome– how to keep the herpes viruses at the tumor site long enough to work.

That is now changing thanks to the work led by Khalid Shah, MS, PhD,which is published in the Journal of the National Cancer Institute. Fun fact, Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.

Shah and his team used mesenchymal stem cells [MSCs]– stem cells that give rise to bone marrow tissue — which was the obvious choice for drug delivery because the immune response they trigger is minimal and could be utilized to carry the virus. So the team loaded the herpes virus into the MSC’s and injected the cells into the tumors [all done in mice mind you]. The team used several imaging markers [which hadn’t really been done in past studies] so they could track the virus as it was passed on to the tumor cells.

“We know that 70-75 percent of glioblastoma patients undergo surgery for tumor debulking, and we have previously shown that MSCs encapsulated in biocompatible gels can be used as therapeutic agents in a mouse model that mimics this debulking,” he continued. “So, we loaded MSCs with oncolytic herpes virus and encapsulated these cells in biocompatible gels and applied the gels directly onto the adjacent tissue after debulking. We then compared the efficacy of virus-loaded, encapsulated MSCs versus direct injection of the virus into the cavity of the debulked tumors.”

[Loony Hint: Debulking is the technical term for removing part or most of the tumor to help increase the effectiveness of chemo or other treatments. It’s good to note that this is used because the full tumor cannot be removed in certain cases.]

Since the team used those imaging proteins I mentioned, the researchers could watch in real time how the virus interacted with the cancer cells. The team noticed that the gel kept the stem cells alive longer, this allowed them to replicate and kill any residual cancer cells that had not been removed. All of which translated into a higher survival rate in the mice models that were treated with the gel-encapsulated stem cells.

Being overachievers, the team also addressed another weakness of cancer-killing viruses–  not all brain tumors are susceptible to the therapy. The solution was to engineer the herpes viruses to express an additional tumor-killing agent, called TRAIL. Again, using mouse models of glioblastoma—this time created from brain tumor cells that were resistant to the herpes virus— the therapy led to increased animal survival.

“Our approach can overcome problems associated with current clinical procedures,” Shah said. “The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors.”

So what’s next? The team is researching ways to use this technique to help treat other types of solid tumors. How long before we can see this treatment? Well, Shah predicts the approach will enter clinical trials within the next two to three years.

Know your Hepatoblastomas from your Retinoblastomas? You probably want the full study — here!

Sources:
Duebgen M., Tamura K., Shah K., Wakimoto H., Redjal N., Martinez-Quintanilla J. & Hingtgen S. (2014). Stem Cells Loaded With Multimechanistic Oncolytic Herpes Simplex Virus Variants for Brain Tumor Therapy, Journal of the National Cancer Institute , 106 (6) DOI:

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One response

  1. yummy

    May 17, 2014 at 2:52 pm

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