Researchers find promise in altered genes to suppress HIV
Genetically modified cells seem to help some patients
Updated 6:35 am, Thursday, March 6, 2014
Scientists safely implanted into HIV-positive patients immune cells that were genetically modified to resist the virus, and the effect for a few of those patients was a decrease in the amount of virus found in their blood - even after they went off drugs that control their infection, according to a study released Wednesday.
The results of the small study, published in the New England Journal of Medicine, intrigued HIV researchers who have been seeking a long-term cure for an infection that requires daily medication.
If the gene therapy treatment proves effective in larger, longer studies, it could offer what's known as a "functional" cure - patients wouldn't necessarily be virus-free, but they would be able to maintain a healthy immune system without daily doses of antiretroviral drugs.
HIV experts said Wednesday that they aren't convinced that the gene therapy technique will lead to such a cure. But the results are a positive sign that the treatment, or others like it, has potential.
'One of the right ideas'
"What this tells us is that (gene therapy) is at least one of the right ideas for HIV infection," said Dr. Mark Kay, a Stanford professor in pediatrics and genetics who was not involved in the study, but who wrote an editorial that was published along with the paper published in the New England Journal of Medicine.
"There's got to be some caution," Kay said. "But this study justifies continuing to look at this approach and trying to make it work more effectively."
The study was conducted at the University of Pennsylvania School of Medicine, using gene therapy technology that was developed by Sangamo BioSciences in Richmond. A dozen patients were given an injection of millions of reprogrammed immune cells.
The treatment proved safe in most cases; one patient had a bad reaction to the transplant that resulted in an emergency room visit for fever, chills and joint and back pain.
Half of the 12 patients in the study were taken off of their antiretroviral drugs to see how their immune systems responded after getting the reprogrammed cells. Two were put back on antiretroviral therapy after eight weeks when the amount of virus started climbing too high. The remaining four were able to maintain a stable level of virus or decrease levels without drug therapy for at least 12 weeks.
The technique involves reprogramming a type of immune cell, called a CD4 T-cell, that is the primary target of HIV. The cells are typically the first to encounter an infection in the body and they trigger an immune response. HIV focuses its attacks on CD4 cells, destroying them and weakening the entire immune system if the virus is left unchecked.
The cornerstone of the new technique is an agent, developed by Sangamo, that blocks a protein receptor in the CD4 cell that makes it vulnerable to HIV.
Building on previous work
Scientists already knew that certain people who lack that receptor, called CCR5, are naturally resistant to HIV infection. One man - who was treated in Germany and now lives in San Francisco - became the first patient to be effectively cured of HIV after he received a CD4-cell transplant from a donor without the CCR5 receptor.
Scientists in the new study, which began five years ago, extracted CD4 cells from the 12 patients, then used the Sangamo agent to reprogram those cells and block the CCR5 receptor. Doctors then re-transplanted patients' own modified cells.
In follow-up tests, the reprogrammed cells survived for at least several months and were much less likely to die off than the patients' untreated cells.
"The limitation is they have to take the cells out of the body, engineer those cells in a test tube, and reinfuse those cells. That's not a scalable approach for the world," Greene said. "But it's an important step."
Scientists from Sangamo are expected to present more long-term results from some study subjects at a conference on retroviruses - including HIV - in Boston on