Made in City of Hope: Neural stem cells could stop brain tumor recurrence

Brain tumors are exceptionally difficult to treat. They can be removed surgically, but individual cancer cells may have already spread elsewhere in the brain and can escape the effects of both radiation and chemotherapy. To prevent tumors from recurring, doctors need a way to find and stop those invasive cancer cells. Researchers at City of Hope think a special type of cell, known as a neural stem cell, could be the answer. Neural stem cells – known for their ability to become any type of cell in the nervous system — not only are attracted to cancer cells, they have the ability to deliver drugs directly to the tumor sites, sparing healthy tissues and minimizing side effects.

A drive to bring discovery to patients

As a researcher at Massachusetts General Hospital and Children’s Hospital, Harvard Medical School, Karen Aboody, M.D., discovered the natural ability of neural stem cells to target cancer cells in the brain. Her pioneering work helped to establish a new field of cancer treatment, one that uses neural stem cells to deliver drugs or other therapies directly to tumor sites.

Aboody came to City of Hope in 2003 specifically for the opportunity to develop this treatment for use in patients. And in 2010, it happened. Jana Portnow, M.D., associate clinical professor, Department of Medical Oncology & Therapeutics Research, led the first-in-human trial of the stem cells, administered to patients whose recurrent brain tumors had not responded to treatment. At the time of their tumor surgery, the patients received a dose of neural stem cells modified to produce a specific enzyme. Next, they were given an inactive pro-drug. Upon reaching the brain and encountering the enzyme produced by the neural stem cells, that pro-drug converted into an active chemotherapeutic agent — in effect, producing localized chemotherapy.

A breakthrough

The results of the pilot trial showed that the stem cells were well tolerated and safe, that they’d migrated to the tumors and that they’d successfully converted the pro-drug to a cancer-killing drug at the tumor sites, sparing healthy cells in the body and brain. These results have paved the way for a pilot safety study, which will establish the appropriate dosing of the therapy.

It could only happen here

Even the most promising discoveries can have trouble moving beyond the laboratory if researchers and clinicians are not trained in translational research. City of Hope supported Aboody’s vision with a team of colleagues, researchers and physicians, as well as manufacturing, administrative and regulatory experts, to help bring neural stem cell-mediated therapy to clinical trial.

The pilot study was funded by the National Institutes of Health’s National Cancer Institute and subsidized by City of Hope. The upcoming phase I trial will be funded by the Food and Drug Administration (FDA) with additional funding from City of Hope. Having access to manufacturing on campus, as well as a hospital facility and patients, further reduces clinical costs.

City of Hope’s existing relationship with the FDA, and the FDA’s familiarity with, and approval of, the manufacturing processes in place at City of Hope’s Center for Biomedicine & Genetics, eased the way for Aboody’s genetically modified stem cells to go into production.

Moving it forward

The phase I brain tumor patient trial, with increased doses and multiple rounds of treatment, is scheduled to start in September of 2014. Aboody and her colleagues will also develop a second generation of stem cells for clinical trial, using an $18 million grant from the publicly funded California Institute of Regenerative Medicine. In this trial, the stem cells will be modified to carry a different drug to brain tumor sites.