City of Hope researchers have begun the first clinical trial of a neural stem cell-based therapy targeting recurrent high-grade gliomas, the most aggressive type of brain tumors.

Karen S. Aboody, M.D., associate professor in City of Hope’s Department of Neurosciences and Division of Neurosurgery, leads the research team that developed the treatment strategy. Jana Portnow, M.D., assistant professor of medical oncology and therapeutics research and assistant director of the Brain Tumor Program at City of Hope, is principal investigator for the clinical trial.

While survival rates vary with the type of brain tumor, patients with glioblastoma, the most common type of glioma in adults, typically survive about 15 months.

Despite surgery, radiation and chemotherapy, the tumors often return. One significant obstacle to curing these tumors is the blood-brain barrier, which can prevent chemotherapy from entering the brain and reaching effective concentrations at tumor sites.

In 2000, Aboody and her colleagues were the first to demonstrate neural stem cells’ tendency to home in on invasive tumor cells, a characteristic known as tropism. Neural stem cells can migrate toward tumors from the opposite side of the brain — or through the blood-brain barrier if delivered intravenously. Aboody’s research team has since harnessed the tumor tropism of neural stem cells to deliver therapeutic agents to tumors and showed the technique’s effectiveness in laboratory testing.

The investigational therapy in the clinical trial uses a genetically modified human neural stem cell line generated by Seung U. Kim, M.D., Ph.D., professor in the Division of Neurology at the University of British Columbia, to deliver an enzyme called cytosine deaminase to brain tumor sites. Physicians then treat patients with 5-fluorocytosine, a relatively nontoxic “prodrug.” Cytosine deaminase converts the prodrug to an active cancer-fighting drug.

The strategy allows concentrated levels of chemotherapy to be activated only in the area of the tumor, minimizing exposure of surrounding healthy tissue and potentially reducing side effects.

“This novel tumor-selective treatment has the potential to overcome many obstacles that limit the success of currently available treatments for malignant brain tumors and other invasive cancers,” said Aboody.

The pilot feasibility study, which assesses neural stem cell doses, is supported by a grant from the National Cancer Institute.

Research Support


Marvin and Sandy Smalley

Long before City of Hope’s neural stem cell research could move into clinical trials, it was a fresh idea in need of funds to move it forward. This vital early support came through a $150,000 seed grant from longtime benefactors Marvin and Sandy Smalley through the nonprofit organization STOP CANCER. Since then, the relationship between supporters and scientist has evolved, and the Smalleys have grown close to Karen S. Aboody, M.D., the physician-researcher who leads this project.

For Sandy Smalley, supporting City of Hope is a family tradition passed down by her parents, longtime members of the Sportsmen’s Club. “It makes me feel really good and close to my parents that we’re still carrying on this tradition and doing something that was very special to them,” she said.

The Smalleys are inspired by City of Hope’s innovation. “City of Hope is not satisfied with resting on their laurels,” added Marvin Smalley. “They’re always looking for something new. They’re very progressive in their thinking and their accomplishments.”

PHOTO BY WALTER URIE