Perfecting the use of stem cells as drug delivery mules shows promise in brain tumors

Stem cells loaded with cancer-killing herpes virus (red) attacking a brain tumor cell (green). Courtesy HSCI

The innate tendency of stem cells to seek out inflammation—combined with the fact that our bodies see tumors as inflammation—has led many teams to try to harness stem cells as delivery vehicles for cancer therapies. CIRM funds a team at City of Hope in Duarte, California that aims to treat brain tumors with stem cells loaded with an agent that can be turned into a form of chemotherapy.

Now, a team at the Harvard Stem Cell Institute and Massachusetts General Hospital have used stem cells to revive a therapy, once considered highly promising, that failed in early clinical trials.

A number of viruses have the ability to kill tumors. In particular, some viruses naturally kill rapidly dividing cells like those found in tumors. But as so often happens, early success in mice did not carry over to the first trials in humans. Researchers reasoned that our body’s immune system cleared out the virus before it could do its deadly deed with the cancer cells.

In this study the Harvard team decided to shield the virus inside stem cells. They then encased the stem cells in a gel that they had previously shown could enhance the ability of the stem cells to remain alive after transplantation.

In a mouse model of glioblastoma, the most common form of brain cancer, the combination extended the life of the mice after the cells were placed at the site where the tumors were surgically debulked, a procedure performed on most human patients with the cancer.

The herpes virus they used had been tagged with an imaging protein that allowed the team to verify that the stem cells lived long enough for the virus to replicate and kill the residual tumor left behind after surgery. It is this residual cancer than makes this brain tumor almost uniformly fatal.

Because a few cancer cells are resistant to the herpes virus, the team gave their killer a second weapon, using genetic engineering techniques to help the virus kill cancer cells. The lead researcher, Khalid Shah, discussed the combination therapy in an article in Genetic Engineering & Biotechnology News:

“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.”

Shah predicted the process would enter clinical trials in two to three years. They published the current research in the Journal of the National Cancer Institute.

Don Gibbons

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