Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital have found a potential solution for how to more effectively kill tumor cells using cancer-killing viruses.
The investigators report that trapping virus-loaded stem cells in a gel and applying them to tumors significantly improved survival in mice with glioblastoma multiforme, the most common brain tumor in human adults and also the most difficult to treat.
The work was led by Khalid Shah, MS, PhD, an HSCI Principal Faculty member. Shah heads the Molecular Neurotherapy and Imaging Laboratory at Massachusetts General Hospital.
Cancer-killing or oncolytic viruses have been used in numerous phase 1 and 2 clinical trials for brain tumors 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 tumor site long enough to work.
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 utilized to carry oncolytic viruses.
Shah and his team loaded the herpes virus into human MSCs and injected the cells into glioblastoma tumors 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 tumor cells and subsequently into all of the tumor cells.
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.
The findings are published in the Journal of the National Cancer Institute.
