The lead clinical trials that are part of the City of Hope Alpha Clinic include:
Altering hematopoietic stem cells (HSC) to fight HIV/AIDS
City of Hope researchers are currently working on two stem cell approaches to fight HIV/AIDS. One method, developed by John J. Rossi, Ph.D., Lidow Family Research Chair and chair of the Department of Molecular and Cellular Biology, is based on gene therapy with small ribonucleic acid (RNA) molecules. These molecules block the genes HIV needs to infect T cells and will be used to modify the patient’s HSCs. The altered stem cells will then be infused into the patient, with the goal of “resetting” the immune system to produce T cells resistant to HIV infection. (COH Protocol #13282)
Another approach, developed by a team of investigators at City of Hope working with Sangamo Therapeutics and Keck School of Medicine at University of Southern California, uses an enzyme called a zinc-finger nuclease. This enzyme acts as a pair of molecular scissors that can edit a single gene in the HIV patient’s HSC that is needed by HIV for infection. The T cells resulting from the genetically modified stem cells will then lack this key protein the virus requires to infect cells. (COH Protocol #14017)
Neural stem cells to help target cancer drugs
Karen Aboody, M.D., professor in the Department of Neurosciences and Division of Neurosurgery and co-leader of the Developmental Cancer Therapeutics Program, in collaboration with Jana Portnow, M.D., associate professor of medical oncology and assistant director of the Brain Tumor Program, have used neural stem cells (NSC) to build a platform to selectively target cancer drugs to tumor sites, potentially increasing efficacy and decreasing side effects. This NSC treatment platform 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 NSC can migrate to brain tumor sites and can be genetically modified to express a therapeutic enzyme. This enzyme could then convert a prodrug – an inactive form of a drug – into a potent cancer-killing drug at the tumor site. Additionally, the prodrug can cross the blood-brain barrier which blocks most chemotherapy drugs, one of the challenges of treating brain cancers. (COH Protocols #13401 and #14108)
CAR T cell for cancer therapy
T cells are part of the immune system that fights and kills cancer cells; however, as cancers progress, they become resistant to the T cell immunity. Researchers are exploring treating a variety of cancers using an approach that genetically modifies the patient’s T cells to recognize and kill a cancer. Patients have their T cells collected from the blood, modified to recognize tumors, expanded to large numbers, and then infused. Upon re-infusion back into the patient, the modified T cells should be able to identify cancer cells and control the cancer. The Alpha Clinic will eventually help advance T cell immunotherapies being developed for a number of cancers. (COH Protocols #13384 and #13272).