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to Section One | to Arts & Entertainment
posted Friday, January 5, 2018 - Volume 46 Issue 01
Genetically modified stem cells may provide HIV cure, study suggests
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Genetically modified stem cells may provide HIV cure, study suggests

by Mike Andrew - SGN Staff Writer

Genetically modified stem cells may be able to suppress - or even eradicate - HIV infections, a new study by a team of researchers based at UCLA suggests.

The study, published on December 28, tested whether genetically engineered cells could be made to kill HIV-infected cells. The method is similar to an FDA-approved gene therapy for cancer.

While the study was small - only using two monkeys and cells grown in lab dishes - it appears to be promising, scientists said.

'The demonstration here that stem cells can be engineered to respond to AIDS virus-infected cells in an animal model is an impressive first step for harnessing the immune system to target HIV,' said Dr. Bruce Walker, director of the Ragon Institute of MGH, MIT, and Harvard, who in the 1990s did pioneering research on the genetic engineering of immune cells to fight HIV and was not involved in the new study.

'The effect at this point is modest but clearly gives us something to build on.'

First, researchers genetically engineered stem cells that produce both the T-cells that attack HIV and other blood cells. The stem cells were then used to produce surface molecules, called chimeric antigen receptors or CARs, on the T cells that are able to recognize and attach to antigens on target cells. That antigen-receptor docking activates the CAR-T cells, causing them to kill the targeted cells.

Researchers were able to create an HIV-specific CAR. One part of the CAR, called CD4, hunts down and binds the HIV, while an additional surface molecule, called C46, interferes with HIV's ability to enter a T cell.

That allowed T cells to detect viruses without being infected themselves. It also let them find and destroy HIV-infected cells, which have some of the same T cell-attracting surface molecules as HIV itself.

The engineered T cells not only destroyed HIV-infected cells in both lab dishes and macaques, they also persisted for more than two years.

That suggests that they can 'provide long-lasting HIV-killing,' said immunologist Scott Kitchen of the David Geffen School of Medicine at UCLA, who led the study published in PLOS Pathogens.

'We think the stem cell approach has greater potential to suppress HIV long-term and even eradicate the virus.'

Clinical trials could begin in a couple of years, Kitchen said. He has been in talks with the private gene therapy company Calimmune and others about developing the approach.

Many barriers to developing a real-world HIV treatment still remain, however.

CAR-T therapy for cancer, using essentially the same clinical approach, is priced at nearly $500,000. An HIV treatment in that price range is clearly out of reach for most of the world, especially poorer countries, which have the majority of HIV/AIDS cases. Some 17 million of the almost 37 million people living with HIV/AIDS aren't even receiving relatively cheap antiretroviral therapy.

Price 'is the main issue here,' Walker cautioned. 'The only real viable role for this kind of therapy would be if it can eliminate the viral reservoir and cure infection, which has not been addressed in this paper. The price tag then could possibly be justified in that case, but given that one can lead a relatively normal life with one pill once a day, it is hard to see how CAR-T cell therapy could be justified just to replace' existing therapies.

Engineered stem cells 'would initially be an expensive approach but would hopefully save the necessity and expense of being on antiretroviral therapy for a lifetime,' Kitchen said. He said he and his colleagues are working on delivering the engineered cells like a vaccine, which might make the treatment more affordable.

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