Investigators from Brigham and Women’s Hospital (BWH) and the Harvard Stem Cell Institute in the United States say they may have discovered a way to kill tumour cells that have metastasized to the brain.
The team developed cancer-killing viruses that can deliver stem cells via the carotid artery and applied them to metastatic tumors. The elimination of metastatic skin cancer cells in mice resulted in prolonged survival, the investigators say.
Khalid Shah, director of the Center for Stem Cell Therapeutics and Imaging (CSTI) in the BWH Department of Neurosurgery, who led the study, said: “Metastatic brain tumors — often from lung, breast, or skin cancers — are the most commonly observed tumors within the brain and account for about 40% of advanced melanoma metastases. Current therapeutic options for such patients are limited, particularly when there are many metastases.
“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.”
In their search for novel, tumor-specific therapies that could target multiple metastases in the brain without damaging adjacent tissues, the research team first developed different BRAF wild-type and mutant mouse models that more closely mimicked what is seen in patients.
They found that injecting patient-derived, brain-seeking melanoma cells into the carotid arteries of the preclinical models resulted in metastatic tumours forming throughout the brain, mimicking what is seen in advanced melanoma cancer patients. The injected cells express markers that allow them to enter the brain and are labeled with bioluminescent and fluorescent markers to enable tracking by imaging technologies.
To devise a potential new therapy, the investigators engineered a population of bone marrow-derived mesenchymal stem cells loaded with oncolytic herpes simplex virus (oHSV), which specifically kills dividing cancer cells while sparing normal cells.
Khalid, who is also a professor at Harvard Medical School and a principal faculty member at the Harvard Stem Cell Institute, said: “We are currently developing similar animal models of brain metastasis from other cancer types, as well as new oncolytic viruses that have the ability to specifically kill a wide variety of resistant tumor cells. We are hopeful that our findings will overcome problems associated with current clinical procedures.”
The study was supported by a Department of Defense Idea Award and a grant from the National Institutes of Health.