New Stem Cell Cancer Treatment is on its way to Human Testing

New Stem Cell Cancer Treatment is on its way to Human Testing
June 2, 2017 

In a previous post, we discussed how removing a glioblastoma tumor—one of the deadliest forms of brain cancer—can actually make the tumor’s remnants grow more quickly. 

You can read the full story here. In that article, we also mentioned that the two lead researchers in that study, Shawn Hingtgen and Ryan Miller from the UNC School of Pharmacy and Lineberger Cancer Center, respectively, were working on a stem cell treatment for glioblastoma.

Neural Stem Cells (blue) in Brain Tissue (Green)

The treatment involved converting skin cells into stem cells and using the stem cells to deliver cancer-killing drugs to the tumor, which worked well using mouse cells, increasing their median survival time by 160 to 220 percent.

The same research group has now advanced this method to work just as effectively with human cells, bringing it one step closer to being tested in human trials. This treatment, published in the journal Science Translational Medicine, could potentially offer a fast, safe and effective option to fight a kind of tumor that affects 20,000 Americans every year.

Glioblastoma is a cancer of the brain’s support cells. It grows rapidly, killing half of the people who have it within 15 months, according to the American Brain Tumor Association, even if those people receive radiation and chemotherapy.

To attack this type of fast-growing tumor, researchers look for a targeted approach, like surgery or drugs that can get into the tumor and attack from the inside.

That's where stem cells come in. The immune system will not see them as a threat, and as the body wants to use them to help in building things, a tumor will suck them up and use them to keep growing. Hingtgen and Miller wanted to use stem cells to infiltrate a tumor, as happens naturally, and then fight the tumor from the inside. They adapted a Nobel Prize-winning method of turning fibroblasts—connective tissue cells that make fibers—into stem cells, so that the stem cell products would specifically grow in the brain and brain tumors.

Interior of a Fibroblast Cell“Speed is essential,” Hingtgen said in a press release. “It used to take weeks to convert human skin cells to stem cells. But brain cancer patients don’t have weeks and months to wait for us to generate these therapies. The new process we developed to create these stem cells is fast enough and simple enough to be used to treat a patient.”

Once inside the tumor, the cells would make and secrete a protein that activates a cancer prodrug: a molecule that does nothing until it is activated, but upon activation kills nearby cells. This way, the drug only becomes active in and around the tumor so healthy tissue does not get caught in the crossfire.

The researchers tested these remade human cells against human glioblastomas that were transplanted in mice. The therapy reduced the size of solid tumors by 250 times, and tumors grown from fragments by 20 times using two different prodrug combinations. When they used the cell therapy on tumors that had been removed, they regrew three times slower than tumors getting normal chemotherapy and radiation.

This translated to doubled survival times when fighting tumors and tumor fragments and a 50 percent increase in survival time when fighting tumor regrowth after surgery. In the mice, that was a matter of weeks, but if those survival ratios hold true in humans, that could mean extra months and years.

Hingtgen says the research is still a year or two away from being ready for human trials, but the fact that the human stem cells were able to perform so well is a promising sign for what would be the first dramatically new treatment for glioblastoma in decades.

—Daniel Lane

Daniel Lane covers science, medicine, engineering and the environment in North Carolina.

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