Re-Engineered Cells Show Promise Against HIV

Scanning electromicrograph of an HIV-infected T cell. (NIAID)

(CN) – Building on a previous attempt, scientists have developed a strategy that could allow a patient’s immune system to more effectively combat HIV, according to findings published Thursday in the journal PLOS Pathogens.

The new approach targets white blood cells known as T cells. T cells play a critical role in the immune system’s response to the virus, particularly once a patient stops taking antiretroviral medications that usually keep the disease under control.

As the virus is capable of evading T-cell attacks, however, some researchers have suggested re-engineering these cells to improve their chances of neutralizing an HIV infection.

While several attempts to re-engineer T cells to fight the virus have been pursued, only one made it to the clinical testing phase and was not ultimately approved for widespread use.

That strategy relied on a chimeric antigen receptor (CAR), a synthetic protein that can be added to T cells to boost their ability to fight a specific foe. During treatment, T cells were extracted from a patient’s blood and re-engineered in a lab to express HIV-specific CARs, before being infused back into the patient.

The PLOS Pathogen study uses recent advances in CAR technology to improve on that approach.

Led by Rachel Leibman, a doctoral candidate at the University of Pennsylvania, the team systematically tweaked different segments of the protein to optimize its effectiveness.

The scientists found that T cells expressing the new CAR were over 50 times more effective at preventing viral spread than those with the original CAR, based on experiments on human cells in the lab.

The researchers also tested the new CAR in HIV-infected mice. During experiments, mouse T cells re-engineered to express the new CAR were able to protect other T cells from being attacked and depleted by the virus. In mice that had been receiving antiretroviral medications, the enhanced T cells delayed the infection’s ability to rebound once treatment was stopped.

These encouraging results could open the door for clinical testing of T-cell re-engineering using the updated CAR, according to the team. If successful, the approach could potentially suppress HIV in the absence of antiretroviral treatment.
“Our data shows for the first time that engineered T cells can significantly control viral rebound in the absence of ART in vivo,” the scientists write. “Our next step is to take this concept forward into the clinic.”

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