HSCI & MGH Attack Brain Tumors With Herpes-Loaded Stem Cells
Harvard Stem Cell Institute (HSCI) researchers at Massachusetts General Hospital report that applying herpes-carrying stem cells to a brain tumor is a potentially more effective and targeted solution to kill brain tumor cells.
The team’s research showed that enclosing virus-loaded stem cell in a gel and putting them on brain tumor cells led to meaningful improvement in the survival of mice with glioblastoma multiforme (GBM). GBM is the most common brain tumor in adults, as well as the most difficult to treat.
Oncolytic herpes simplex viruses show potential against tumors as they naturally infect dividing brain cells. However, until now, scientists have been stumped over how to keep the herpes virus at the tumor site until their oncolytic work is finished.
Khalid Shah, an HSCI Principal Faculty member and leader of the study, used mesenchymal stem cells (MSCs) to carry oncolytic viruses. MSCs also induce minimal immune response, making it a viable drug delivery vehicle. The scientists used multiple image markings to observe the virus as it passed from the stem cells to the first layer of brain tumor cells, eventually infecting all 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. 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,” said Professor Shah.
The researchers found that the gel kept the stem cells alive for a longer time and bought time for the virus to replicate and kill any remaining cancer cells during the debulking surgery. The cells were also made to express an additional tumor killing agent named TRAIL for brain tumors resistant to herpes virus. The approach encouraged a higher rate of survival for mice models that received the gel-encapsulated oncolytic cells and TRAIL-expressing stem cells.
“Our approach can overcome problems associated with current clinical procedures. The work will have direct implications for designing clinical trials using oncolytic viruses, not only for brain tumors, but for other solid tumors,” Professor Shah said. He predicted that the approach will be tested in clinical trials within the next two to three years.
The researchers’ work is published in the Journal of the National Cancer Institute.