As scientists across the globe race to find a cure for HIV, researchers in Pittsburgh say they have developed an immunotherapy method that can “kick and kill” the latent virus in infected cells.
By adapting the immune system’s own defenses, scientists at the University of Pittsburgh were able to detect latent HIV lying dormant in cells, reactivate it, and then eliminate the cells.
Detailing their findings in EBioMedicine, the scientists said that the key to their approach lies in engineering immune cells designed to recognize a different virus — Cytomegalovirus (CMV), which can cause eye infections and other illnesses.
However, unlike HIV, CMV can be contained by a healthy immune system and doesn’t require treatment.
The Pittsburgh team adapted cells known as dendritic cells, which senior author Robbie Mailliard, Ph.D., likened to the quarterbacks of the body’s defense systems. “They hand off the ball and dictate the plays, telling other immune cells where to go and what to fight,” Mailliard told UMPC.com.
Researches used blood samples from men who are living with HIV and using antiretroviral treatments (ART) to procure cells that contained latent HIV.
While taking ART, HIV enters a dormant phase where the virus attaches itself to immune system cells known as T helper cells. If a person stops taking ART, the dormant virus reactivates, and if left untreated can then progress to AIDS.
Finding and eliminating the dormant cells that contain the virus would ensure that a person who stopped talking ART wouldn’t succumb to HIV.
“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,” Mailliard said. “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.”
To seek out HIV, researchers adapted the dendritic cells (MDC1) to find T helper cells that contained latent CMV. Their theory was that, alongside CMV, they might also find latent HIV.
As researchers expected, HIV was indeed lying dormant in the CMV-infected cells, with the engineered MDC1 cells reactivating the latent virus.
But beyond just detecting the virus, the engineered MDC1 cells also recruited the immune system’s own defenses to eliminate the HIV-infected cells — or, kick and kill.
“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.”
The research could eventually lead to a cure for those living with HIV, allowing the immune system to find and destroy HIV before it can regain control.
The team now plans to secure funding to progress the treatment to clinical trials.
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