The first FDA-approved gene therapy treatment for cancer patients has shown promise in suppressing HIV infection long term in lab monkeys, according to a study partially funded by amfAR.
Researchers genetically engineered stem cells to express chimeric antigen receptors (CAR) that can detect and destroy SHIV (a combination of HIV and SIV—the monkey form of the virus). The cells were then tested in four male juvenile SHIV-infected macaques.
Not only did the engineered cells decrease the viral load, they persisted for more than two years in the monkeys without any adverse effects. Furthermore, the cells were widely distributed throughout the lymph nodes and gastrointestinal tract, where viral replication and persistence are concentrated.
“The advantage of the stem cell-based approach is that once these cells are grafted into the body, they continuously produce new T cells that have this gene in them that can target HIV cells,” said amfAR grantee Dr. Scott Kitchen of the University of California, Los Angeles.
The FDA approved the gene therapy treatment Kymriah in August 2017 for young people up to age 25 with a form of acute lymphoblastic leukemia, a blood cancer. The therapy involves modifying a patient’s own T cells and genetically engineering them with CAR cells that can recognize and kill tumors.
Its approval coincided with the announcement of two amfAR grants exploring a similar strategy to curing HIV.
Commenting on the study for HealthDay, Dr. Marcella Flores, amfAR’s associate director of research, said she was cautiously optimistic about the potential of gene therapy to eradicate the virus. “CAR therapy is already leading to impressive results in cancer,” she said.
However, she noted that the study was performed in monkeys. Results in humans may be quite different.
Kitchen said human trials could begin within two to three years. While it is unlikely that the CAR strategy will work completely on its own, he said it could be used with antiretroviral therapy to engineer an immune response to target and kill HIV.
“Theoretically the goal is to provide lifelong immunity to HIV,” he said. “We’re aiming for a cure, and we know that to cure HIV you need an effective immune response.”
The study was published in the December 28 issue of PLOS Pathogens.