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HIV Exposed and Destroyed by Immunotherapy Using Common Virus

Engineered MDC1 Cells Reverse Latency

Scientists from the University of Pittsburgh Graduate School of Public Health announced in EBioMedicine their development of an all-in-one immunotherapy that not only kicks HIV out of hiding in the immune system but kills it. The key lies in immune cells designed to recognize a completely different virus.

The discovery, made using cells from people with HIV, remains to be tested in clinical trials, but could eventually lead to a vaccine that would allow people with HIV to eliminate their daily medication regimen to keep the virus at bay.

While a person with HIV is taking daily antiretroviral therapy (ART) medications, the virus goes into an inactive phase and incorporates itself into the DNA of “T helper cells.” If the person stops taking the ART drugs, the virus can turn into full-blown AIDS.

The team decided to look at another virus that goes quiescent and infects more than half of adults–– including 95% of those with HIV––cytomegalovirus (CMV), which can cause eye infections and other serious illnesses but is usually controlled by a healthy immune system.

In some people, one of every five T cells are specific to CMV, according to the researchers. Entertaining the possibility that the cells fighting CMV also constitute a large part of the latent HIV reservoir, they engineered their immunotherapy to target HIV as well as activate CMV-specific T helper cells.

In addition to the T helper cells, they isolated dendritic cells, which are crucial in cancer immunotherapy. Although these cells have previously been used to prompt the immune system to kill HIV, they had not been utilized to “pull” latent HIV out of hiding. The researchers engineered “antigen-presenting type 1-polarized, monocyte-derived dendritic cells” (MDC1) to find and activate CMV-specific cells, believing they could also contain latent HIV.

When the MDC1 cells were added back to the T helper cells containing latent HIV, they reversed that latency and exposed the virus. Those MDC1 cells then went on to recruit killer T cells and eliminate the infected cells.

The researchers believe theirs is the first study to program dendritic cells to incorporate CMV and get both “kick and kill” results. They now hope to secure funding for clinical trials in order to test this property of MDC1 in humans.

Source: University of Pittsburgh Graduate School of Public Health, April 3, 2019

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