Duke investigators are part of a team that has designed a protein that could someday cure HIV.
The Dual-Affinity Re-Targeting protein is a bi-specific antibody, meaning it was engineered to bind to two types of molecules simultaneously—HIV-infected cells and T-cells, which are the body’s frontline defense system. By bringing HIV-infected cells close to T-cells, the DART protein would make it easier for the immune system to eliminate HIV from patients’ bodies. Although medical researchers have already developed treatments to prevent those who are HIV-positive from exhibiting symptoms, the scientific community has yet to come up with a cure for the disease.
Early study results have been promising thus far, and Macrogenics—a biotech company with investigators working alongside researchers from Duke and the University of North Carolina at Chapel Hill—has obtained a contract from the National Institutes of Health to begin human clinical trials in approximately one year.
“We can’t cure AIDS because the virus inserts itself into the genetic material of the person that is infected and then goes into hiding. It’s invisible to the immune system and invisible to the otherwise effective drugs that control the disease,” explained Dr. Barton Haynes, senior author of the study describing the DART molecule in the Journal of Clinical Investigation and the director of the Duke Human Vaccine Institute. “So the goal is to figure out ways to find those invisible cells and to ferret them out and to kill them.”
The DART protein is designed to do just that. Haynes explained that DART antibodies are shaped like the letter Y. One arm of this Y binds to HIV infected cells, while the other arm binds to killer T-cells, which destroy any cells they come into close contact with. By bringing killer T cells into contact with HIV-infected cells, the DART protein helps the body rid itself of the HIV virus.
Despite the potential benefits of the protein in curing HIV, Haynes also noted that it poses risks.
“Anytime you try to get the body’s immune system to turn on itself and to eliminate either a cancer cell or a virus infected cell, if that kind of activity goes too much, then it has a chance of harming the body,” he explained. “So the body tends to err on the side of turning down the immune system and preventing this kind of thing from happening.”
Although there are concerns regarding backlash from the immune system, the tests done on lymphocytes from human patients so far have demonstrated that the response does not significantly affect the treatment, explained Dr. Julia Sung, lead author of the study and clinical assistant professor of medicine at UNC.
“In the paper we just published in September, we did not come across that in any of the patients we studied,” Sung said. “I am sure that in every patient there was a subset of T-cells that didn’t do what the DARTs were trying to make them do, but because there’s such a large number of T-cells present in the body, there still were enough to get the job done.”
The researchers so far have seen promising results from testing the DART molecules in vitro, or in test tubes. They are preparing to start testing DART proteins in animals, Haynes said. If those tests also yield positive results, investigators will be able to move on to clinical trials and start testing the proteins in HIV-infected individuals. Haynes added that Scott Koenig, president and CEO of MacroGenics, has recently received a contract with the NIH to begin human trial testing soon.
Although medications have already been developed to prevent those infected with HIV from developing AIDS, the treatments available today come with significant drawbacks, including their exceedingly high price. The Center for Disease Control estimates the lifetime cost of HIV medications to be $367,134 per patient, though different states have different policies on how this cost is distributed between the patients and insurance companies.
Sung added that some strains of HIV are simply resistant to medication, and even the strains that do respond to treatment do not always respond fully. The virus, though suppressed, will still put the patient at increased risk of developing cancer or having heart attacks and strokes.
In addition, patients taking HIV medication have to remember to take the drug every day, Sung said. This caveat poses a problem, especially with younger groups of patients, such as those infected in utero.
Despite the obstacles, Sung said the investigators are looking forward to expanding on the initial research.
“It’s a really exciting time to be in the HIV eradication field and in particular it’s been a great time to work in a productive collaboration between the industry with MacroGenics and between the two academic institutions of Duke and UNC,” she said.