Radioactive antibodies hunt out HIV-infected cells

For decades researchers have wondered what it would take to eliminate the immunodeficiency virus HIV from a patient's body. Now they think that radioactive antibodies might do the trick. Scientists from the United States and Germany have combined antibodies that seek out cells infected with HIV with radioactive payloads that can destroy them, as they report in the 6 November issue of PLoS Medicine. Harris Goldstein at the Albert Einstein College of Medicine in New York, who led the team, says the new approach might be used to kill HIV-infected cells soon after a person is infected, in an attempt to stop the virus establishing a permanent beachhead in the body. Such a treatment would probably be used in conjunction with the current drug treatment known as highly active antiretroviral therapy (HART). But it could also be used long after a person has been infected, perhaps together with therapeutic drugs — still in their experimental phase — that aim to flush HIV out of the redoubts in which it sequesters itself and make it more visible to the immune system. "This is not a cure for HIV," Goldstein says. "This is a new concept for targeting HIV-infected cells and eliminating them." Goldstein and his team tested their approach in cell cultures and in mice. First, the team constructed its weapons: radioactive chemicals joined to antibodies that recognize particular proteins displayed only on the surface of an HIV-infected cell. In tissue-culture experiments, the antibodies killed most of the HIV-infected cells. The researchers then tested the radioactive antibodies in mice that had been specially engineered so that they contain human immune cells that HIC infects. The mice were infected with HIV and then injected with radiolabelled antibodies. The team found that the antibodies eliminated up to 99% of the HIV-infected cells from the mice, although the dose needed for almost total elimination was higher than that likely to be used in humans. Now, the team is trying to find a company that will test its approach in a clinical trial. Similar ideas have been tried before: toxins have been attached to antibodies, for example, in the hope that the toxins would destroy HIV-infected cells. That didn't work, but as radioactive antibodies are already used to treat certain cancers, the researchers hope that the new approach might also work for HIV. "One advantage to this approach is that there's a significant body of work already in radioimmunotherapy for cancer cells, and this is sort of a cancer therapy approach to this problem, which may be what we need," says David Margolis, an HIV specialist at the University of North Carolina at Chapel Hill, who was not involved in the new work. The main questions will be whether the new approach works in people, and whether it has toxic side effects. The main side effect is likely to be the accidental killing of cells not infected with HIV. The scientists behind this study said they didn't see evidence of toxicity in the mice, based on platelet counts in their blood, but only clinical trials will determine whether the same holds true in people. "http://www.nature.com/news/2006/061106/full/061106-1.html":[ http://www.nature.com/news/2006/061106/full/061106-1.html]

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