Research scientists may have figured out how to destroy the most common brain tumor in human adults, which also happens to be the most difficult to treat. Researchers at the Harvard Stem Cell Institute (HSCI) at Massachusetts General Hospital found that by trapping herpes-loaded stem cells in a gel and applying them to tumors, they were able to significantly improve the survival rate of mice with glioblastoma multiforme brain tumors.
The study, which is published in the Journal of the National Cancer Institute, is an improved-upon version of the previous cancer-killing methods for brain tumors and is predicted to enter human trials within the next two to three years. In past preclinical studies, oncolytic herpes simplex virus has been shown to naturally infect dividing brain cells, however it never worked well when tested on human patients. Researchers weren’t able to keep the herpes virus at the tumor site long enough for it to effectively kill the brain tumor, until now.
If you’ve ever had a cold sore or fever blister, you have picked up the common viral infection known as herpes simplex. They come in the form of one of more painful fluid-filled blisters, which break open and often ooze fluid before they heal within one to two weeks. Herpes-simplex type 1 can cause break outs on the lips, tongue, or around the mouth, while herpes-simplex type 2 will cause break outs on the penis, vagina, buttocks, or anus. The virus targets and destroys cancer cells because of the high levels of protein found in tumors, however, researchers have been unable to prove the therapy’s safety, which will likely be a lengthy process.
This time around researchers decided to try mesenchymal stem cells (MSCs), a known drug vehicle that could be used to deliver the herpes virus into the glioblastoma tumors in mice. With the use of multiple imaging markers, scientists were able to watch in real time how the herpes virus passed from the stem cells to the first layer of brain tumor cells, and eventually throughout the entire tumor cells. The gel was able to keep the stem cells alive long enough to kill any cancer cells that aren’t removed in debulking surgery, which is the surgical removal of a tumor.
"We know that 70 to 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," said Khalid Shah, the study’s lead author, in a press release. Shah is an associate professor at Harvard Medical School, and head of the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.
"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said. “Comparison studies showed that the naked virus rarely infects the residual tumor cells. This could give us insight into why the results from clinical trials with oncolytic viruses alone were modest."
A weakness of the approach, according to the study, indicated that not all brain tumors were susceptible to the gel-intact oncolytic herpes virus. Researchers created another therapy solution called “TRAIL” to kill brain tumors other than glioblastoma, which increased animal survival.
Shah predicts that after further preclinical work has been performed, herpes-loaded stem cells will become an applicable treatment for breast, lung, and skin cancer tumors that migrate to the brains. The approach, as Shah hopes, will enter clinical human trials within the next two to three years.
Duebgen M, Martinez-Quintanilla J, Tamura K, Hingtgen S, Redjal N, Wakimoto H, and Khalid S. Stem Cells Loaded With Multimechanistic Oncolytic Herpes Simplex Virus Variants for Brain Tumor Therapy. Journal of the National Cancer Institute. 2014.