Toxin-producing stem cells fight brain tumors where it matters most
When it comes to new tumor-fighting treatments, it’s often as much about location, location, location as it is the actual drug interaction. Cytoxin-producing stem cells produced by scientists at Harvard University lodge at the site of brain tumor removal to continually attack remaining tumor cells. As an alternative to drug treatments that can be invasive or ineffective, the researchers saw promising results against glioblastomas, which hold the dubious distinction of being the most common and most fatal brain cancer.
When surgery is performed to remove a brain tumor, tumor cells are left behind. The common course of treatment to eradicate those remaining cells involves inserting a catheter directly into the brain to dispenses drugs which would otherwise not make it through the blood-brain barrier. However, one particular toxin, Pseudomonas exotoxin (PE), while effective and tolerated by humans, has a very short half-life and when washed over the area where the tumor was removed, degrades before significant interaction occurs with the target cells.
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The research team under the direction of Khalid Shah instead created stem cells that were capable of independently producing this cytotoxin. Prior to this research, PE and other toxins had been engineered to not enter (and thus subsequently destroy) any human cells they came into contact with. However, Shah’s stem cells would need to have this resistance when the toxin was by design already inside the cell.
After genetically constructing a stem cell that produced a toxin that it also could resist, the next design trick involved encapsulating those cells inside a gel matrix that the lab had previously used to test other tumor-fighting techniques. Their previous research found that the matrix kept the cells and resulting toxins in close proximity to the tumor cells.
This cell-doped gel can then be placed within the cavity created when a tumor is removed and could potentially remove the need to insert catheters for recurring drug treatments. To test this technique, mice first were given different strains of glioblastomas, which is important because not all strains respond in the same way to treatments. Researchers then removed the tumors and inserted the stem cell matrix.
When mice treated in this fashion were compared with those who received the same drug via catheter, and those mice who only had surgery, median survival for those three groups fell out significantly in favor of the stem cell group at 79 days versus 48 for those receiving catheter treatment, and 26 for the control. Additionally, no tumors regrew in those mice with the stem cell matrix, a result not seen in the other groups.
The treatment could have some promising applications, such as engineering cells to dispense multiple toxins, or even based directly off the patient’s tumor. Shah predicts there could be clinical trials for this technique within five years.
The research was originally published in the journal Stem Cells.
Source: Harvard University