Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have a potential solution for how to more effectively kill tumour cells using cancer-killing viruses.
The work, led by Khalid Shah, an HSCI Principal Faculty member, found that trapping virus-loaded stem cells in a gel and applying them to tumours significantly improved survival in mice with glioblastoma multiforme, the most common brain tumour in human adults and also the most difficult to treat.
Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumours but with limited success.
In preclinical studies, oncolytic herpes simplex viruses seemed especially promising, as they naturally infect dividing brain cells.
However, the therapy hasn't translated as well for human patients. The problem previous researchers couldn't overcome was how to keep the herpes viruses at the tumour site long enough to work, researchers said.
Shah and his team turned to mesenchymal stem cells (MSCs) - a type of stem cell that gives rise to bone marrow tissue - which have been very attractive drug delivery vehicles because they trigger a minimal immune response and can be utilised to carry oncolytic viruses.
Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumours developed in mice.
Using multiple imaging markers, it was possible to watch the virus as it passed from the stem cells to the first layer of brain tumour cells and subsequently into all tumour cells.
"We know that 70-75 per cent of glioblastoma patients undergo surgery for tumour 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 said.
"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 tumours," said Shah.
Using imaging proteins to watch in real time how the virus combated the cancer, Shah's team noticed that the gel kept the stem cells alive longer, which allowed the virus to replicate and kill any residual cancer cells that were not cut out during the debulking surgery.
This translated into a higher survival rate for mice that received the gel-encapsulated stem cells.
"They survived because the virus doesn't get washed out by the cerebrospinal fluid that fills the cavity," Shah said.
The research is published in the Journal of the National Cancer Institute.