Khalid Shah

Brigham researchers have found an unlikely ally in the fight against brain cancer: viruses.

It can be challenging to treat more than one tumor in the body, and cancers that spread to the brain are especially difficult to treat. That’s because the same membrane preventing substances in the blood from entering the brain also prevents many therapies, such as chemotherapy, from breaching what’s known as the blood-brain barrier.

In a new study published in PNAS, researchers from BWH and the Harvard Stem Cell Institute identified a potential solution for how to kill cancer cells that have metastasized – that is, spread – to the brain. Their strategy? Delivering cancer-killing viruses that can selectively target, infect and replicate within cancer cells. The team tested this treatment using skin cancer cells in a preclinical model that closely mimics what is seen in advanced melanoma patients.

When injected on their own, these cancer-killing viruses are unable to locate cancerous brain tissue. To overcome this limitation, the research team packaged the “anti-tumor viruses” inside stem cells and delivered them via the carotid arteries (major blood vessels in the neck that supply blood to the brain, neck and face) in a preclinical tumor model.

The stem cells track tumor deposits and act as a cellular vehicle to deliver the viruses directly to tumor cells. The population of stem cells used in this study were derived from human bone-marrow and loaded with oncolytic herpes simplex virus (oHSV), which specifically kills dividing cancer cells while sparing normal cells.

Like hunting dogs following a scent, these stem cells loaded with oHSV sniffed out the tumor cells and began destroying them as intended. Researchers reported that this treatment led to significant decreases in the number of metastatic cancer cells and prolonged survival in these preclinical models.

Khalid Shah, MS, PhD, director for the Center for Stem Cell Therapeutics and Imaging in the Department of Neurosurgery, who led the study, says that metastatic brain tumors – often from lung, breast or skin cancers – are the most commonly observed tumors within the brain and account for 40 percent of advanced melanoma metastases.

“Current therapeutic options for such patients are limited, particularly when there are many metastases,” Shah said. “Our results are the first to provide insight into ways of targeting multiple brain metastatic deposits with stem-cell-loaded oncolytic viruses that specifically kill dividing tumor cells.”