July 7, 2015 | by City of Hope
A gliobastoma patient has become the first person to be treated by City of Hope's new Alpha Clinic for Cell Therapy and Innovation (ACT-I), heralding a potential breakthrough in the treatment for brain tumors and in the use of stem cells.
“Glioblastoma is the most aggressive-behaving, malignant primary brain tumor, and new treatments that target cancer cells in the brain are desperately needed,” said Jana Portnow, M.D., associate professor of medical oncology and associate director of the Brain Tumor Program at City of Hope, who is leading the current phase I neural stem cell study.
The patient underwent surgery for recurrent glioblastoma and was then treated in a clinical trial using genetically-modified neural stem cells – which naturally home to cancer cells – to help deliver chemotherapy to brain cancer cells. The aim of this neural stem cell research is to develop a treatment that is more potent and less toxic than existing treatments for brain tumors.
“We’ve genetically modified these cells to produce chemotherapy at the sites of the tumor in the brain,” said Karen S. Aboody, M.D., professor in the Department of Neurosciences and Division of Neurosurgery and co-leader of the Developmental Cancer Therapeutics Program at City of Hope. “Rather than putting chemotherapy through the whole body and possibly causing significant side effects that affect quality of life, the neural stem cells produce active chemotherapy only at the sites of the tumor, killing surrounding cancer cells.”
Stem cells and pro-drug work together
In the study, which has now accrued several patients and continues to enroll, neural stem cells have been genetically modified to carry an enzyme that converts a pro-drug – a harmless form of a drug – to a powerful chemotherapy agent. The stem cells are administered directly to the brain, and three days later, the patient takes a seven-day course of the pro-drug. Once the pro-drug crosses the blood-brain barrier, the stem cells convert it to the chemotherapy drug at the sites of the tumor.
That type of breakthrough research is what the statewide CIRM Alpha Clinics Network was meant to do, said John Zaia, M.D., the Aaron D. Miller and Edith Miller Chair in Gene Therapy and principal investigator of the ACT-I clinic at City of Hope. In addition to the City of Hope clinic, the California Institute for Regenerative Medicine, or CIRM, has funded clinics at University of California Los Angeles, University of California Irvine and University of California San Diego. The goal is to make stem cell based treatments a reality for patients battling catastrophic diseases, including cancer, AIDS, diabetes, spinal injury, blindness and heart disease.
“Alpha clinics like ours aim not only to provide research to benefit patients in the future, but also to bring these treatments to real-life clinics where nurses and other staff members will become familiar now with technologies that hopefully will benefit patients in the near future,” Zaia said.
Building on the encouraging results of a previous first-in-human safety trial, the trial will allow patients to receive more than a single dose of the therapeutic stem cells. To deliver the drug, a catheter is placed in the brain at the time of surgery for administering repeated doses of the cells every two weeks.
Behind the research: Californians and CIRM
The new phase I trial comes a decade after Californians voted to found CIRM, making a commitment to investigating stem cell therapies in the laboratory. Now these therapies are ready for human trials. Future ACT-I trials at City of Hope will include stem cell therapy for AIDS, T cell immunotherapy for blood cancers and brain cancer, and treatments for breast cancer metastases and ovarian cancer treatments.
Zaia said the clinic also plans to work with City of Hope’s diabetes researchers to ultimately introduce treatments for diabetes, exploring both the potential of pancreatic stem cells and preventing the immune system from attacking insulin-producing cells.
“We are delighted that, just months after the launch of the Alpha Stem Cell Clinics Network, City of Hope’s ACT-I team has recruited staff and treated its first patients and has been able to provide clinical trial support for this very specialized protocol,” said Maria Millan, M.D., CIRM medical director. “But this work does more than help just one person. Because they are part of the Alpha Clinics Network, City of Hope is demonstrating how by working together, providing collective expertise, efficiencies and critical resources, we can help accelerate the development of stem cell treatments for patients with unmet medical needs. This is the start of something truly unique.”
CIRM funded the clinic with an $8 million, five-year grant that will be supplemented by matching funds from City of Hope.
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