Researchers from the University of Pittsburg report a new “all-in-one” immunotherapy approach that could lead to a new vaccine to help HIV-positive people to fight the virus without having to take daily medications.
Their new approach exploits another virus, Cytomegalovirus (CMV), which typically causes eye infections and other serious illnesses, to draw HIV into the open. CMV is present in more than half of adults and 95% of those infected with HIV. It’s usually kept in check by an otherwise healthy immune system.
“The immune system spends a lot of time keeping CMV in check; in some people, one out of every five T cells (white blood cells that fight illness) are specific to that one virus,” said Charles Rinaldo, Ph.D, a professor and chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology, via 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.”
In other words, doctors found T cells that fighting CMV are also infected with HIV. They then researched how to safely destroy these HIV-infected T cells using another immune system defense: dendritic cells, a white blood cell that marks infected cells for destruction.
To test their theory, researchers brought in two dozen people from the Pitt Men’s Study to collect enough blood for the test. The Pitt’s Men’s Study is the Pittsburgh location for the Multicenter AIDS Cohort Study (MACS), a research study focused on the natural history of treated and untreated HIV/AIDS in gay and bisexual men.
“The MACS participants were vital to the success of this study,” said researcher Jan Kristoff. “You have to collect a lot of blood to find T cells latently infected with functional HIV in people on ART (anti retroviral treatment) — 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.”
Kristoff also isolated dendritic cells, which can be used to kill HIV in patients. As researcher Robbie Mailliard describes them, “They hand off the ball and dictate the plays, telling other immune cells where to go and what to fight.”
Dendritic cells are also used in cancer immunotherapies; Mailliard had previously worked on research using dendritic cells to fight melanoma.
Researchers used, “antigen-presenting type 1-polarized, monocyte-derived dendritic cells,” or MDC1, to seek out and activate the CMV-specific cells. By drawing those cells out, they were able to draw latent HIV hiding within them.
“Without adding any other drug or therapy, MDC1 were then able to recruit killer T cells to eliminate the virally infected cells,” said Mailliard. “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 currently raising funding to begin clinical trials in humans.