Gene therapy may kill HIV

Gene therapy may have the potential to eradicate HIV in people infected with the virus, new animal research suggests. The science centers around the use of "chimeric antigen receptor" (CAR) genes. In laboratory work with monkeys, these engineered cells have destroyed HIV-infected cells for more than two years, scientists reported.

T-cells are the cells that are largely responsible for human ability to fight off pathogens and get rid of infections in the body. Every T-cell has a unique receptor, or molecule, on it. That receptor allows the cell to recognize a specific target-a bacteria, or fungus or virus. And when it recognizes that target, it's called into duty to clear it from the body. Taking artificial receptors- CAR that can go on to these cells and allow them to recognize what we want them to recognize," he noted. "In this case that's HIV."

First, the team genetically engineered CAR to find and bind to simian/human immunodeficiency virus (SHIV), a lab-engineered HIV hybrid composed of human virus and monkey virus. Then the researchers modified the DNA of certain blood-forming stem cells so they would carry SHIV-killing CAR. The resulting cells were introduced into the bloodstream of four male juvenile SHIV-infected macaque monkeys.

The engineered cells successfully took up residence in each monkey's bone marrow. The cells moved widely throughout the body, targeting and killing SHIV-infected cells, without producing any notable adverse side effects. The advantage of the stem cell-based approach is that once these cells are grafted into the body, they continuously produce new T-cells that have this gene in them that can target HIV cells.

Plans are underway for a human trial, this study shows both that these cells will respond to HIV and that it's safe. This strategy is unlikely to fully work on its own, CAR will most likely need to be used with antiretroviral therapy. CAR therapy is already leading to impressive results in cancer and holds promise for HIV eradication.
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Gene therapy can destroy HIV infected cells

Through gene therapy, researchers engineered blood-forming stem cells (hematopoietic stem/progenitor cells, or HSPCs) to carry chimeric antigen receptor (CAR) genes to make cells that can detect and destroy HIV-infected cells. These engineered cells not only destroyed the infected cells, they persisted for more than two years, suggesting the potential to create long-term immunity from the virus that causes AIDS.

Antiviral drugs can suppress the amount of HIV in the body to nearly undetectable levels, but only an effective immune response can eradicate the virus. Researchers have been seeking a way to improve the body's ability to combat the virus by engineering blood-forming stem cells to specifically target and kill HIV-infected cells for the life of the individual.

 Although chimeric antigen receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer -- and show promise in treating HIV-1 infection -- the therapy may not impart long-lasting immunity. Researchers, physicians and patients need T cell-based products that can respond to malignant or infected cells that may reappear months or years after treatment.

Because HIV uses CD4 to infect cells, the researchers used a CAR molecule that hijacks the essential interaction between HIV and the cell surface molecule CD4 to make stem cell-derived T-cells target infected cells. When the CD4 on the CAR molecule binds to HIV, other regions of the CAR molecule signal the cell to become activated and kill the HIV infected cell.

The researchers found that, in test animals, modification of the blood-forming stem cells resulted in more than two years of stable production of CAR-expressing cells without any adverse effects. In addition, these cells were widely distributed throughout the lymphoid tissues and gastrointestinal tract, which are major anatomic sites for HIV replication and persistence in infected people. Most important, engineered CAR T-cells showed efficacy in attacking and killing HIV-infected cells.
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