At Case Western Reserve University, researchers have discovered an immunotherapy approach to treat Acquired Immunodeficiency Syndrome (AIDS). Published in mBIO, a scientific journal by the American Academy of Microbiology, this research aims to reduce the need for lifelong AIDS medication.
For decades, AIDS, the end stage of an untreated Human Immunodeficiency Virus (HIV) infection, was a fatal diagnosis. Now, thanks to antiretroviral therapy (ART), it has become a manageable chronic condition. Modern drug combinations can suppress the virus to undetectable levels, allowing people living to lead long, healthy lives without risk of transmission. However, ART does not cure AIDS and requires lifelong, strict adherence to medication along with a myriad of side effects.
The challenge lies in the virus’s ability to hide.
“[HIV is] in a family of retroviruses, which means the viral genome that gets transmitted is an RNA, but once it gets into [human] cells, the RNA gets converted into double stranded DNA,” said Jonathan Karn, the director of CWRU’s Center for AIDS Research.
The virus then inserts its DNA into the host cell genome permanently, where it may either remain in an active state and produce more virus particles or enter a reversibly dormant state in HIV reservoirs, a population of long-lived infected immune cells.
“So if you stop taking drugs, the virus rebounds,” Karn said.
To expose and eliminate these hidden HIV reservoirs, Karn’s laboratory is harvesting the power of Natural Killer (NK) cells. These white blood cells (WBCs) in the immune system are the first line of defense against viral infections and cancer.
“NK cells from people living with HIV have an innate ability to kill HIV-infected cells, but this requires activation,” said Mary Ann Checkley-Luttge, a senior research associate in the Department of Molecular Biology and Microbiology at CWRU School of Medicine. “The idea is that activated NK cells more easily find and kill actively infected cells than latently infected cells, thus reducing reservoirs enough to allow long-term immunological control of HIV without ART.”
Karn’s lab is using approaches already developed from cancer immunotherapy to enhance the ability of NK cells, making this the first time these techniques have been used for HIV therapy.
“NK cells can be extracted from the blood and grown to large numbers in the laboratory in presence of feeder or artificial antigen presenting cells (aAPCs), [which are genetically engineered WBCs that present a signaling protein to amplify NK cells],” Checkley said. “The boosting of NK cells with this approach also increases activating receptors in NK cells which help them recognize cells that need to be killed.”
While this study was performed on cells from people living with HIV, the Karn lab is also using Macaque models to understand the impact on whole-body systems. In collaboration with Temple University and Rutgers University, the results from these animal models will be applied to developing clinical trials in people living with HIV in the upcoming years.