(KDKA/CBS Local)–Scientists at the University of Pittsburgh Graduate School of Public Health have developed an all-in-one immunotherapy approach that not only kicks HIV out of hiding in the immune system, but also kills it.
The results were reproted in EbioMedicine on Wednesday.
Researchers say the key lies in immune cells that are designed to recognize an entirely different virus.
The results came from a laboratory setting and used cells from people with HIV. It has yet to be tested in clinical trials but scientists say it could lead to the development of a vaccine that would allow people positive for HIV to stop taking daily medications to keep the virus in check.
“A lot of scientists are trying to develop a cure for HIV, and it’s usually built around the ‘kick and kill’ concept – kick the virus out of hiding and then kill it,” said senior author Robbie Mailliard, Ph.D., assistant professor of infectious diseases and microbiology at Pitt Public Health. “There are some promising therapies being developed for the kill, but the Holy Grail is figuring out which cells are harboring HIV so we know what to kick.”
Scientists say that (ART) or Antiretroviral therapy typically controls HIV infections so well that the virus is virtually undetectable in the blood and cannot easily infect other people.
But if a person with HIV stops taking the daily regimen of medications, which come with many side-effects, the virus can rage back and turn into full-blown AIDS. This is because the virus goes into a latent, inactive phase where it incorporates itself into the DNA of certain immune cells called “T helper cells,” and lurks while a person is taking ART.
Mailliard and his team decided to look at a different virus that also goes latent and infects more than half of adults – and 95 percent of those with HIV: Cytomegalovirus (CMV), which can cause eye infections and other serious illnesses, but is usually controlled by a healthy immune system.
Researchers say nearly two dozen people participated in the study by giving blood, and often would have to sit for as long as four hours, or come back multiple times.
“The MACS participants were vital to the success of this study,” said first author Jan Kristoff, M.S., a doctoral candidate at Pitt Public Health said. “You have to collect a lot of blood to find T cells latently infected with functional HIV in people on ART – it could be as few as 1 out of every 10 million cells. So the men would sit for as long as four hours hooked up to a machine that processed their blood and came back multiple times to give more samples.”
In addition to the T helper cells, Kristoff also isolated immune cells called dendritic cells, which Mailliard describes as the quarterbacks of the immune system: “They hand off the ball and dictate the plays, telling other immune cells where to go and what to fight.”
Dendritic cells are key to cancer immunotherapies, and Mailliard previously worked on a team developing such a therapy being used to treat melanoma. Conventional dendritic cells also have been used to induce the immune system to kill HIV. But they hadn’t yet been exploited to “kick,” or pull latent HIV out of hiding in the body. In this study, the team engineered “antigen-presenting type 1-polarized, monocyte-derived dendritic cells” (MDC1) that were primed in the lab to seek out and activate CMV-specific cells, with the thinking that they also may contain latent HIV.
When the MDC1 were added back to T helper cells containing latent HIV, they reversed that latency as expected, kicking the virus out of hiding. And then the big test came.
“Without adding any other drug or therapy, MDC1 were then able to recruit killer T cells to eliminate the virally infected cells,” Mailliard said. “With just MDC1, we achieved both kick and kill – it’s like the Swiss Army knife of immunotherapies. To our knowledge, this is the first study to program dendritic cells to incorporate CMV to get the kick, and also to get the kill.”
UPMC says the team is now pursuing funding to begin clinical trials in humans.