One of the greatest challenges in treating cancer is figuring out how to eradicate tumor cells without harming healthy ones. This is particularly true for cancers that affect major organs such as the lungs, the liver or the brain. A study conducted by a team of neuroscientists at Harvard University and led by Khalid Shah, a professor at Harvard Medical School, poses a potential solution to the problem of distinguishing between cancer cells and normal, healthy ones.
The research uses human neural stem cells modified in the laboratory to secrete cell toxins, to target specific molecular “tags” on the surface of certain cancer cells. These markers often arise as mutations from the markers on normal cells, used for signaling and identification among different cell types.
This kind of “targeted therapy” differs from traditional chemotherapy in that it hones in on different cells using the same molecular cues that the body’s organs and cells already rely on. Other therapies mainly target the rapid growth that is characteristic of many late-stage cancer cells, but this can be problematic because similar growth can also occur in many of the body’s normally fast-growing cells, such as hair cells.
Shah’s team introduced two mutations in the DNA of the stem cells, which are remarkably receptive to these changes because of their ability to differentiate into every kind of cell in the human body. One of these mutations incorporated the genetic codes for several cytotoxin proteins, proteins that are toxic to cells. Introduction of the mutation allowed the cells to transcribe, produce and express the toxins autonomously. The other mutation induced immunity of the stem cells to the toxins used, as undifferentiated stem cells still express all of their genes — including those that potentially code for the same targeted markers on cancer cells.
These two mutations, combined with a capsule of a biodegradable gel applied around the altered stem cells, allow for a much more efficient and cleaner targeting of cancer cells.
Previous clinical trials involved attempts to deliver the cytotoxins in their molecular form directly to the site of the tumor but failed because of the drugs’ short half-life and the difficulty in reaching deeper or more solid masses in the brain. The new stem cells are not merely a vehicle for the toxins; in a way, they are the drug themselves.
After surgically removing the main bulk of brain tumors in mice, the neuroscientists introduced the stem cell and gel mixture into the vacated resection cavity. Magnetic resonance imaging and chemical analysis revealed the death of cancer cells and a decrease in protein synthesis directly around the cavity. Both of these results indicate that the toxin has successfully entered only remaining cancer cells, disrupting these cells’ ability to produce proteins required for normal function and thus inducing death.
Clinical trials for the stem cells are currently in the process of being approved by the Food and Drug Administration. In the meantime, Shah plans to examine the combined effects of the toxin-modified stem cells and stem cells injected with a form of the herpes simplex virus that he identified as a potential cancer-fighting agent earlier this year. This virus, a variation of the virus that causes the disease of the same name, naturally infects dividing brain cells and interferes with their growth. The herpes virus, combined with the selectivity of the genetically modified stem cells, could become a revolutionary approach to the scientific fight against brain cancer.
