Center for Gene Therapy Clinical Trials

Altering patient cells 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 molecules. These molecules block the genes HIV needs to infect T cells, and are used to modify the patient’s hematopoietic stem cells. The altered stem cells are infused into the patient, with the goal of “resetting” the immune system to produce T cells resistant to HIV infection. So far, this approach has been tested in three clinical trials: COH Protocol #04047 (NCT00569985), COH Protocol #13282 (NCT01961063) and COH Protocol #14004 (NCT02337985).

Another approach, developed by a team of investigators at City of Hope working with Sangamo Therapeutics and Keck School of Medicine of USC, uses an enzyme called a zinc-finger nuclease. This enzyme acts as a pair of molecular scissors that can edit a single gene (CCR5) in the HIV patient’s blood stem cells 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 them (COH Protocol #14017, NCT02500849

Developing a cure for adults with severe sickle cell disease

This clinical research involves the use of mixed chimerism — transplanting blood stem cells from a half-matched family member into a sickle cell disease patient who has received a less toxic form of chemotherapy. Prior to the transplant, the donor stem cells are depleted of CD4+ T cells, which provides a more hospitable environment within the patient and reduces his or her chances of developing graft-versus-host disease (GVHD), a common side effect of transplantation (COH Protocol #16453, NCT03249831).
Another Pilot study assesses whether blood stem cells from SCD patients can be safely mobilized from the bone marrow to the peripheral blood for future gene therapy (COH Protocol #17426, NCT03664830).