November 16, 2014 | by Nicole White
Identifying cures for currently incurable diseases and providing patients with safe, fast and potentially lifesaving treatments is the focus of City of Hope’s new Alpha Clinic for Cell Therapy and Innovation (ACT-I).
The clinic is funded by an $8 million, five-year grant from the California Institute for Regenerative Medicine. The award is part of CIRM’s Alpha Stem Cell Clinics program, which aims to create one-stop centers for clinical trials focused on stem cell treatments for diseases.
Two trials were identified to launch the center, but additional trials are currently enrolling patients and will be part of this clinic. The first trials center on transplants of blood stem cells that have been modified to treat patients with AIDS and lymphoma, and on the use of neural stem cells – which naturally home to cancer cells – to deliver drugs directly to cancers hiding in the brain. Coming soon will be trials that use T cell immunotherapy, developed by researchers in City of Hope’s new Hematologic Malignancies and Stem Cell Transplantation Institute.
“We are committed to finding cures and treatments to diseases that are, for now, incurable,” said John Zaia, M.D., the Aaron D. Miller and Edith Miller Chair in Gene Therapy, chair of the Department of Virology and principal investigator for the stem cell clinic. “This grant recognizes City of Hope’s commitment to and leadership in this endeavor, as well as enables us to pursue the crucially important work of bringing the promising potential of stem cell treatments to fruition.”
In addition to the Alpha Stem Cell Clinic grant, City of Hope has previously been awarded more than $55 million in CIRM funds for laboratory and translational research, primarily in HIV/AIDS and brain cancer.
Potential new ways to fight AIDS
City of Hope scientists are currently investigating two different means of altering stem cells to fight AIDS. One approach is a combination of stem cell and gene therapy using small ribonucleic – or RNA – molecules that block the genes HIV needs to infect immune cells, specifically T cells. Developed by John Rossi, Ph.D., Lidow Family Research Chair and chair of the Department of Molecular and Cellular Biology, this approach aims to spur the immune system to produce T cells resistant to HIV by infusing the patient with these altered stem cells.
Another approach uses an enzyme called a zinc-finger nuclease, or ZFN, as a pair of molecular scissors that can edit the HIV patient’s stem cell genes so they no longer produce a key protein the virus requires to infect cells. This approach has been developed by a team of investigators at City of Hope working with Sangamo Biosciences and Keck School of Medicine at USC.
Karen Aboody, M.D., professor in the Department of Neurosciences and Division of Neurosurgery, co-leader of the Developmental Cancer Therapeutics Program and principal investigator of a CIRM Disease Team Award, in collaboration with Jana Portnow, M.D., associate professor of medical oncology and associate director of the Brain Tumor Program, developed a neural stem cell platform for targeting cancer drugs selectively to tumor sites, potentially increasing efficacy and decreasing side effects.
This platform also will be available through clinical trials offered by the Alpha Clinic. In previous laboratory and first-in-human safety trials, Aboody and her team established that neural stem cells genetically modified to express a therapeutic enzyme migrated to cancer cells. These enzymes could then convert a prodrug – a benign form of a drug – into a potent cancer-killing drug at the tumor site. The prodrug itself can cross the blood-brain barrier which blocks most chemotherapy drugs, one of the challenges of treating brain cancers.
On the frontier of T cell immunotherapy
The new clinic will eventually help advance T cell immunotherapies being developed for a number of cancers through the Hematologic Malignancies and Stem Cell Transplantation Institute, led by Stephen J. Forman, M.D., director of the T Cell Immunotherapy Research Laboratory. Researchers are exploring treating a variety of cancers using a similar approach: Patients have their T cells collected from the blood, then modified using a lentivirus – a retrovirus that encodes the tumor recognition information into the T cell. The modified cells are able to identify proteins found on cancer cells – and, researchers believe, the immune system will now be able to fight the cancer.
City of Hope’s proposal was the most highly ranked application for this round of Alpha Stem Cell Clinic Awards in which the top the projects were scored.
“Everything we do has one simple goal, to accelerate the development of successful treatments for people in need,” said C. Randal Mills, Ph.D., president and CEO of the stem cell agency. “Stem cell therapies are a new way of treating disease; instead of managing symptoms, cellular medicine has the power to replace or regenerate damaged tissue and organs. And so we need to explore new and innovative ways of accelerating clinical research with stem cells. That is what we hope these Alpha Stem Cell Clinics will accomplish.”