Immunotherapy Method Seeks to 'Kick and Kill' HIV

Investigators at the University of Pittsburgh School of Public Health have created a comprehensive immunotherapy treatment approach that exposes HIV through the immune system and destroys it by allowing immune cells to recognize the virus.

Senior study author Robbie Mailliard, PhD, at Pitt Public Health, explained that current HIV treatments center around the “kick and kill” method, in which the virus is kicked out of hiding and killed after it is isolated.

“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,” Dr. Mailliard said in a press release.

Antiretroviral therapy (ART) typically controls HIV infections so effectively that the virus is undetectable in the blood and cannot easily infect other people. The therapy works by making the virus latent, or inactive, so that it incorporates itself into the DNA of certain immune cells, called T-helper cells, according to the press release. When a patient suffering from HIV stops their daily ART regimen, the virus can advance into AIDS.

In order to understand this process, the investigators studied cytomegalovirus (CMV), which causes eye infection and other serious infections but is usually regulated by a healthy immune system.

"The immune system spends a lot of time keeping CMV in check; in some people, 1 one out of every 5 T cells are specific to that one virus," co-author Charles Rinaldo, PhD, professor and chair of Pitt Public Health's Department of Infectious Diseases and Microbiology, said in a press release. "That got us thinking -- maybe those cells that are specific to fighting CMV also make up a large part of the latent HIV reservoir. So, we engineered our immunotherapy to not only target HIV, but to also activate CMV-specific T helper cells."

The study included approximately 24 participants from the Pitt Men’s Study, the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS), which researched the natural history of treated and untreated HIV/AIDS in men who have sex with men.

In addition to T-helper cells, the investigators isolated immune cells known as dendritic cells, which act as messengers between immune systems, indicating what to fight and when. Conventional dendritic cells have been used previously to induce the immune systems to kill HIV, but have yet been exploited to kick or isolate latent HIV.

This study engineered antigen-presenting type 1-polarized, monocyte-derived dendritic cells (MDC1), which were primed in the lab to seek out and activate CMV-specific cells, in hopes they also may contain latent HIV, according to the press release.

"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 team is now pursuing funding to begin clinical trials to test this property of MDC1 in humans.

Reference

• Immunotherapy kicks and kills HIV by exploiting a common virus [new release]. Published April 4, 2019. https://www.sciencedaily.com/releases/2019/04/190404104413.htm. Accessed April 16, 2019.