HIV is a sneaky virus. It can hide in the immune cells of people taking daily antiretroviral therapy (ART) drugs, waiting until they stop the therapy to come back with a vengeance. OMG!
In a study published Tuesday in the journal EBioMedicine, the Pitt team details how it engineered an immunotherapy called MDC1 to target both HIV and Cytomegalovirus (CMV), a virus that infects 95 percent of people with HIV.
“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,” researcher Charles Rinaldo said. “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.”
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.”
The plan worked, with MDC1 sussing out the latent HIV in infected blood and then killing it.
The discovery, made in the laboratory using cells from people with HIV, is yet to be tested in clinical trials, but 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.
CREDIT: Donna Stolz, Ph.D./University of Pittsburgh, Center for Biologic Imaging