September 18, 2011

Altered T cells reduces the amount of HIV virus in infected people

Sangamo BioSciences of Richmond, California, says it has found a way to protect the T cells that HIV attacks first, so they can live to fight another day. The approach entails temporarily stopping a patient's antiretroviral therapy and removing T cells carrying the CD4 receptor. This surface protein is the doorway by which the virus gains entry into the cell. The collected T cells are exposed to zinc finger nuclease, an enzyme designed to remove the gene for a coreceptor of CD4 called CCR5. The cells are then reinfused into the patient. Once they're back in the body, the new study shows, the cells persist and travel in the body just like normal T cells.

Sangamo's approach is based on the observation that some people have a naturally occurring mutation in the CCR5 gene that protects them against HIV. Ordinarily, humans have two copies of every gene. It turns out that individuals with a mutation in both copies of the CCR5 gene cannot be infected by the most common HIV strains. In people with the so-called Delta-32 mutation in just one copy of the gene, infection rarely progresses to AIDS. In the U.S., about 1 percent of the population is thought to carry the helpful mutation, which some researchers believe arose as protection against the Black Death.

Previous evidence existed showing that CCR5-negative cells could help AIDS patients. In 2007, an American man with AIDS and lymphoma received, as treatment for the cancer, a bone-marrow transplant from a person with the CCR5 mutation. The marrow recipient has been free of both AIDS and cancer since then. Sangamo's method treats a patient's own cells, with less risk than a marrow transplant.




Experts unaffiliated with Sangamo and its clinical trials agree that the scientific achievement is impressive, but they question the notion that it could yield a functional cure.

Sangamo is also exploring the potential of stem-cell modification with City of Hope researchers, but the company does not concede that modified stem cells will be necessary or any better than T cells. "Yes, T cells turn over," says Geoff Nichol, who joined Sangamo as executive vice president of R&D a few months ago to commercialize the platform, "but there are some very long-lasting subsets that can live for years and years and remember the epitope they came up against. We are feeling bullish about T cells because of our data."

Sangamo's news is "certainly scientifically interesting," observes Warner Greene, director of the Gladstone Institute at the University of California, San Francisco. But, he points out, no cell therapy, whether it involves T cells or stem cells, is a practical approach to treating HIV/AIDS throughout the developing world, where seven out of 10 new infections are occurring. "We really need to be looking for therapies that can benefit the millions of individuals with HIV, not just a select few who might be able to afford cellular therapies."

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