State Stem Cell Agency Approves Research Funding for UC Davis Scientists

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Pair of research grants target solid tumor cancer stem cells, Tay-Sachs disease

Two new UC Davis research efforts, one aimed at addressing fatal early childhood conditions known as Tay-Sachs and Sandhoff disease, the other designed to develop an immunotherapy that would eradicate solid tumor cancer stem cells and create sustained anti-tumor effects, have been approved for funding by the California Institute for Regenerative Medicine (CIRM).

William Murphy, professor of dermatology and internal medicine, and a specialist in cancer immunology, is leading a team that plans to target tumor cancer stem cells in aggressive malignancies such as breast cancer, pancreatic cancer and sarcomas. Working with colleague Robert Canter, associate professor of surgery, Murphy will use an immunotherapeutic cell product derived from placental stem cells to eradicate cancer stem cell populations in patients.

Joseph Anderson, an assistant adjunct professor of internal medicine and a stem cell researcher, is working to develop a therapy that would halt the progression of Tay-Sachs (and its more severe form, Sandhoff) disease, which is a rare, inherited and incurable disease that affects an infant’s central nervous system.

CIRM funding for the two projects, which together total more than $3.2 million, were part of the state stem cell agency’s highly competitive Translational awards approved during this week’s board meeting in San Mateo.

“The goal of our Translation program is to support the most promising stem cell-based projects and to help them accelerate that research out of the lab and into the real world, such as a clinical trial where they can be tested in people,” said Jonathan Thomas, chair of the CIRM Board. “The projects that our board approved today are a great example of work that takes innovative approaches to developing new therapies for a wide variety of diseases.”

Murphy’s proposal noted that cancer continues to be a major cause of death in the United States despite a wide range of cancer therapies. He and his research colleagues have found that natural killer (NK) cells have intrinsic properties suited to attack cancer stem cells, the cells often responsible for cancer recurrence and its spread to distant organs. They are combining NK cells with traditional treatments such as radiation therapy to simultaneously attack the dividing cancer cells as well as the cancer stem cells. That approach already has led to collaboration with the UC Davis School of Veterinary Medicine, where clinicians are using it to treat pet canines suffering from sarcomas (one of the most common cancers in dogs).

The innovative proposal also addresses the current reliance on isolating NK cells from a patient’s, or healthy donor’s, blood. It turns out that placenta-derived stem cells (stem cells derived from medical waste after birth) are also an excellent source of NK-like cells. Murphy and colleagues suggest these NK-like cells would be an ideal source of “off-the-shelf” cancer stem-cell-targeting cells and may have unique advantages compared to standard NK cells, such as being able to survive for longer periods of time in the body and combining more effectively with traditional cancer therapies such as radiation therapy and targeted antibody treatments.

Anderson’s translational research project, which received crucial seed funding from the Cure Tay-Sachs Foundation, targets a rare but devastating disease that over time causes nerve cells in the brain and spine to die. Sandhoff disease, the more severe form of the condition, leaves babies with none of the enzymes necessary to break down fatty substances in cells, including brain cells. Without enough of the enzymes, fatty substances build up, slowly destroying brain cells and causing the nervous system to stop working. The two disease forms have no cure or effective treatment.

Anderson plans to combine gene therapy with specially engineered hematopoietic or blood-forming stem cells, to create a therapy that could rescue the affected neurons and halt disease progression.

“There is a critical need to develop better treatments for cancer, as well as rare diseases that currently have no cure,” said Jan Nolta, director of the UC Davis Stem Cell Program and the university’s Institute for Regenerative Cures. “If our researchers can demonstrate success with their innovative approaches to developing new therapeutic candidates, it will also open the door to stem cell therapies for other disorders and diseases. Each step moves us forward in regenerative medicine.”

With the two latest CIRM grants, UC Davis has now earned 44 awards totaling more than $130 million in funding from the stem cell agency.

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Charles Casey
UC Davis Institute for Regenerative Cures
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