By Darrin S. Joy and Shawn Le
HIV is a crafty and pernicious germ. Uncanny in its ability to outsmart vaccines and other tried-and-true antiviral treatments, this infection remains incurable. But the writing’s on the wall.
|Researchers are a step closer to protecting T cells from HIV infection, as shown above. (Photo credit National Institutes of Health)|
City of Hope researchers have demonstrated the first successful, long-term persistence of anti-HIV genes in patients with AIDS-related lymphoma treated through gene therapy.
The breakthrough marks a major step toward giving HIV-positive patients lasting resistance to the virus — something not currently available.
“While highly active antiretroviral drugs have managed to turn HIV infection from an immediate death sentence to a long-term manageable chronic condition, we are still seeking a cure,” said David DiGiusto, Ph.D., professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation (HCT). “Our research and clinical trials are showing promise for this novel approach to treating HIV patients.”
In the experimental treatment, HIV-positive lymphoma patients underwent autologous HCT, which is standard therapy for lymphoma. Patients’ own blood stem cells were collected, purified and reinfused; however, researchers pulled aside some cells and modified them. The altered cells produced three genetic molecules that block HIV from infecting new cells.
This gene therapy strategy was developed by City of Hope’s John J. Rossi, Ph.D., Lidow Family Research Chair and chair of City of Hope’s Department of Molecular and Cellular Biology. It uses molecules of ribonucleic acid, or RNA — a close relative of DNA — designed to target and block specific genes that HIV needs to infect cells and reproduce.
The goal of the therapy is to reboot the immune system, so it can identify HIV, mount a response to the infection and lower the amount of virus in the blood.
To check if the therapeutic genes took hold in the stem cells, the researchers took blood samples from each patient over the course of two years and checked to see if the new genes were still there.
“We still see evidence that the patients are producing the therapeutic genes … as long as two years after transplant,” said John A. Zaia, M.D., Aaron D. and Edith Miller Chair in Gene Therapy and chair of the Department of Virology at City of Hope. He leads the human clinical trial of the therapy.
The gene therapy research eventually may yield a cure for both the cancer and the HIV infection. The team continues research and clinical trials to improve the efficiency of their process, so future patients can receive even more of the genetically modified stem cells to boost their resistance to HIV.