In a small trial, researchers have successfully used gene therapy to boost the immune system of 12 patients with HIV to resist infection. They removed the patients' white blood cells to edit a gene in them, then infused them back into the patients. Some of the patients who showed reduced viral loads were off HIV drugs completely.
In fact, one of the patients showed no detectable trace of HIV at all after therapy. The researchers, who report their phase I study in the New England Journal of Medicine believe theirs is the first published account of using gene editing in humans.
The team included researchers from the University of Pennsylvania (Penn), PA, Albert Einstein College of Medicine, Bronx, NY, and Sangamo BioSciences, Richmond, CA, the company that developed the gene editing technology.
Carl H. June, senior author of the study and professor at Penn's Perelman School of Medicine, says:
"This study shows that we can safely and effectively engineer an HIV patient's own T cells to mimic a naturally occurring resistance to the virus, infuse those engineered cells, have them persist in the body, and potentially keep viral loads at bay without the use of drugs."
He says the findings reinforce their belief that editing T cells is the key to eliminating the need for lifelong antiretroviral drugs (ADTs). It could even lead to "functional curative approaches for HIV/AIDS," he adds. A functional cure means there are no detectable traces of the disease in the patient.
The gene editing method they used is called "zinc-finger nuclease (ZFN)" - a sort of molecular scissors.
They used ZFN to edit a gene called CCR5 in immune T cells to make it like a mutation that occurs in 1% of the population. People with the mutation, called CCR5-delta-32, are naturally resistant to HIV. The mutation effectively blocks the way the virus enters immune cells.
Each patient received an infusion of 10 billion modified cells
For the study, the team infused the patients' own modified T cells back into them. Each received a single infusion, containing about 10 billion cells, between May 2009 and July 2012.
Starting 4 weeks after infusion, six of the patients were taken off antiretroviral therapy altogether for up to 12 weeks, while the other six remained on treatment.
The purpose of a phase I trial is to test safety and how well patients tolerate the treatment. The researchers report the infusions were safe and tolerable, and modified T cells continued to persist in the patients during follow-up visits.
The trial also showed the technique shows promise in ability to suppress HIV. The viral loads fell in four patients whose treatment was interrupted for 4 weeks.
One patient's HIV viral load fell below detectable levels
Also, in one of the patients, the viral load fell below the limit of detection - the researchers could find no trace of HIV in the patient's body. They later discovered this patient already had one natural copy of the CCR5 gene mutation.
Co-author Bruce L. Levine, a professor in cancer gene therapy, explains:
"Since half the subject's CCR5 genes were naturally disrupted, the gene editing approach was building on the head start provided by inheriting the mutation from one parent. This case gives us a better understanding of the mutation and the body's response to the therapy, opening up another door for study."
The next step is to test the therapy with more patients using larger numbers of modified T cells and improved ways of helping more cells persist in the body to achieve as near to a functional cure as possible.
The National Institute of Allergy and Infectious Diseases (NIAID), the Penn Center for AIDS Research, Clinical Trials Unit, and Sangamo BioSciences funded and supported the study.