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Stem-cell Therapy Holds Promise for Eliminating HIV Infection

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David Geffen School of Medicine

U Magazine

Scientists at the UCLA Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research are one step closer to engineering a tool to arm the body’s immune system to fight — and win — against HIV. The new technique harnesses the regenerative capacity of stem cells to generate an immune response to the virus.

“We hope this approach can one day allow HIV-positive individuals to reduce, or even stop, their current HIV drug regimen and clear the virus from the body altogether,” says Scott Kitchen, PhD, associate professor of medicine in the Division of Hematology and Oncology. “We also think this approach could possibly be extended to other diseases.”

Dr. Kitchen and his colleagues are the first to report the use of an engineered molecule called a chimeric antigen receptor (CAR) in blood-forming stem cells. The researchers inserted a gene for a CAR into blood-forming stem cells in the lab, which then were transplanted into genetically engineered HIV-infected mice. The researchers found that the CAR-carrying blood stem cells successfully turned into functional T cells that could kill HIV-infected cells in the mice. The result was an 80-to-95 percent decrease in HIV levels, strongly suggesting that stem-cell-based gene therapy with a CAR may be a feasible and effective treatment for chronic HIV infection in humans.

UCLA scientists are engineering T cells to locate and kill HIV-infected cells. Graphic: Mirabai Vogt

“Despite the increased scientific understanding of HIV and better prevention and treatment with available drugs, a majority of the 35-million people living with HIV, and millions more at risk of infection, do not have adequate access to prevention and treatment, and there is still no practical cure,” says Jerome Zack, PhD, co-director of the UCLA AIDS Institute and associate director of the UCLA Broad Stem Cell Research Center. “With the CAR approach, we aim to change that.”

Previous studies by Drs. Kitchen and Zack demonstrated similar results with other T-cell receptors, although it is known that HIV could mutate away from those receptors. Another shortcoming of T-cell receptors used in earlier clinical studies was that they could not be universally used in patients because they would have to be individually matched to patients — in the same way organs are matched to transplant recipients.

Dr. Kitchen says the CAR approach is more flexible, and potentially more effective, because it could theoretically be employed in anyone. If further testing continues to show promise, the researchers hope a treatment based on their approach could be brought to human clinical trials within five-to-10 years.

“Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector,” Molecular Therapy, April 14, 2015

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