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A Cure for HIV? Cancer-Killing Immunotherapy Could Also Fight the Virus
 
 
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By Kate Sheridan On 1/3/18 at 4:06 PM
 
http://www.newsweek.com/cure-hiv-cancer-killing-immunotherapy-could-also-fight-virus-769703
 
Genetically modifying stem cells to produce HIV-fighting blood may someday be possible, according to a new paper published in PLOS Pathogens on Tuesday.
 
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"Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS"....http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006753

 
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In the paper, researchers implanted modified hematopoietic stem cells-in other words, cells that make blood-in two monkeys. The blood cells being made included immune system cells, like infection-fighting natural killer, or NK, and T cells. The researchers watched to see if the stem cells would stay alive inside the monkeys and if they would start producing cells that could attack cells infected with a form of HIV.
 
For more than two years, modified versions of blood cells were produced in the animals-which is a good sign. This kind of technique is called chimeric antigen receptor therapy, but it's better known by the acronym CAR-T.
 
Modifying stem cells with CAR therapy is a big advance, says study author Scott Kitchen, a researcher at the David Geffen School of Medicine at the University of California, Los Angeles. "In order to eradicate the virus, you really need an effective immune response. Because HIV attacks the immune response, that's difficult to achieve," he told Newsweek. But in theory, that's what this treatment could do. "This is step one, basically showing that we can modify stem cells, that you can get lifelong cells produced." However, using CAR therapy to treat HIV in humans may still be far in the future, according to James Riley, an immune system and HIV researcher at the University of Pennsylvania's Perelman School of Medicine who was not involved in the research. Some of the results were relatively subdued, he noted. Only one of the two animals that received the treatment showed a decrease in the amount of virus circulating in its blood compared to animals that did not receive the treatment. However, the amount of virus in the blood of the other monkey did still decrease compared to its own starting point.
 
Regardless of how effective the approach may be, completing a human study would require "heroic efforts," said Riley. Even for more traditional stem cell transplants, the process can be difficult. The study does prove that it's possible to generate these cells, implant them into monkeys and launch an attack on HIV in a way that maintains the stability of the animal. But, says Riley, using this kind of technique in people will require more work.
 
From HIV to Cancer to HIV
 
Interestingly, CAR-T, which has been making headlines for its anticancer benefits, was originally intended for the 37 million people living with HIV today. According to an article in the New England Journal of Medicine, CAR-T pioneer Carl June had been working on a way to modify the immune cells in HIV patients for most of his career until his wife was diagnosed with ovarian cancer.
 
That diagnosis changed the course of CAR-T research. About twenty years ago, June switched his focus to cancer. In August, the Food and Drug Administration approved the first-ever CAR-T treatment for human cancer.
 
For now, CAR therapies are mostly useful for blood cancers because the proteins on the surface of blood cells provide an obvious target for T-cells to attack. However, scientists are actively looking for ways to target other kinds of cancers.
 
This group is far from the only one looking into new ways to attack HIV. In October, researchers in Australia announced a new way to sniff out where copies of the virus might be hiding-a key step toward eliminating detectable disease in people who have been infected. Other researchers are working on tools to help scientists replicate the success seen in one person after a bone marrow transplant. Still others are studying how existing cancer drugs might work to "shock and kill" copies of the virus.
 
If this technique does wind up being a viable treatment-or even a cure-for HIV, that doesn't guarantee that it will eradicate the disease. The price tag could stand in the way. As Sharon Begley notes in STAT, CAR-T doesn't come cheap. The company behind a CAR-T treatment, Kymriah, is charging $475,000. (And that's just for the treatment. As Kaiser Health News reported, there are a number of other costs that surround CAR-T that wouldn't be included in that price.)
 
Human Studies
 
But that's getting way ahead of things. The next step Riley sees for this particular treatment would be to move into humans-despite the relatively modest results. And Kitchen is planning on a first-in-human trial with people who have their virus suppressed. "We anticipate having this in human trials in the next two to three years," he said.
 
That study could be considered ethically tricky. HIV is no longer an immediate threat to a person's life, and doing this kind of procedure would be an extreme measure compared to the treatments that exist today. "If you'd done this approach 20 years ago or 30 years ago, you might have been able to go straight to the clinic with it because there were no good approaches to treat it," Riley said. That's not true anymore. "The only thing you can do now is cure HIV. That's a very high bar."
 
To bypass some of the ethical concerns about trying a high-risk treatment in humans, Riley suggested people might consider introducing it as part of a stem-cell transplant for another disease, like some blood cancers. "Ethically, that would be the ideal patient population for a first-in-human trial. That would show some proof of principle in humans, which I think is what you're really going to need to do to move this forward." "In the end, you're not really going to know if this is going to work or not work until you try this in humans," said Riley.

 
 
 
 
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