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| Encapsulated toxin-producing stem cells (blue) kill brain tumor cells (green).--Courtesy of Khalid Shah |
Scientists have figured out a way to harness stem cells so that they can be used to produce and emit toxins capable of killing brain tumors.
The stem cells, genetically engineered by Harvard Stem Cell Institute researchers at Massachusetts General Hospital, were effective at destroying cancer cells left behind in mouse brains after the main tumor had been surgically removed.
The achievement could pave the way for new treatments for glioblastoma, the most common brain tumor in human adults. Glioblastoma is often treated with a combination approach, such as removal of the tumor followed up with radiation and chemotherapy, because some cells in these tumors respond to treatment while others may be impervious to medical interventions.
Neuroscientist Khalid Shah led the research, which is detailed in the journal Stem Cells. Shah has recently shown that stem cells loaded with herpes viruses may also prove an effective foe against brain cancer.
"Cancer-killing toxins have been used with great success in a variety of blood cancers, but they don't work as well in solid tumors because the cancers aren't as accessible and the toxins have a short half-life," said Shah, who directs the Molecular Neurotherapy and Imaging Lab at Massachusetts General Hospital and Harvard Medical School, in a statement.
After the brain tumor is taken out, the stem cells are placed at the removal site encapsulated in a biodegradable gel. This method solves a delivery issue that may have contributed to the failure of recent clinical trials that attempted to deliver purified cancer-killing toxins into patients' brains, according to Shah.
Shah's stem cells are genetically engineered to have a certain mutation that gives them the ability to deliver therapeutic toxins to the brain without being themselves being killed by the toxins. This extra genetic code is what allows the stem cells to secrete toxins called cytotoxins. Cytotoxins are toxic to all cells, but scientists have figured out how to manipulate them so that they only enter cancer cells with specific surface molecules, leaving normal cells intact. Once the cytotoxin makes it inside of a cell, the toxin disrupts an essential proteinmaking mechanism inside the cell, triggering cell death.
Next, Shah plans to try out the toxin-secreting stem cells in different combinations with various therapeutic stem cells developed by his team to test which have the most beneficial effects in mouse models of glioblastoma. Shah and his team are also pursuing clinical trials and hope to win FDA approval for the treatment.
- get the study abstract
- read the press release