Wednesday, November 08, 2006
The new approach to AIDS therapy -- called radioimmunotherapy -- works in mice, report Ekaterina Dadachova, PhD, of New York's Albert Einstein College of Medicine, and colleagues.
"Radioimmunotherapy is supposed to be curative," Dadachova tells WebMD. "Current HIV treatments kill the virus, but it will come back because it hides in latently infected cells. Our goal is to go after those cells, so radioimmunotherapy has the potential to cure somebody completely."
Dadachova's colleague, Harris Goldstein, MD, tempers his enthusiasm a bit more. Goldstein is director of the Einstein/MMC Center for AIDS Research in New York.
"If we had a nickel for every time HIV was cured we'd all be very wealthy," Goldstein tells WebMD. "But it is exciting when a new conceptual approach comes along. What makes this treatment unique is that it is designed to target HIV infected cells and kill them. This really has the potential to markedly reduce the viral infection in patients."
What has Dadachova and Goldstein so excited is their finding that the new AIDS therapy concept works not just in the test tube, but in living animals.
The treatment starts with an antibody that homes in on a piece of HIV (called gp41) that sticks out of HIV-infected cells. The antibody is attached to a radioactive isotope. It latches on to cells carrying HIV and irradiates them. Since the antibody doesn't stick to healthy cells, the treatment doesn't affect them.
This may sound like the future, but such treatments already exist. The FDA-approved drugs Zevalin and Bexxar are radioimmunotherapies that target cancer cells in people with non-Hodgkin's lymphoma.
Recently, Dadachova, Goldstein, and others showed that radioimmunotherapy could be used to treat infections as well as cancers. In their new study, they show that the technique can seek out and destroy human HIV infected cells growing in specially bred mice.
"Many things fail in animals that worked in the test tube," Goldstein says. "So the antibodies being able to hunt out and eliminate HIV infected cells brings this a lot closer to the clinic."
Indeed, the researchers hope to begin human clinical trials within two years.
It's an innovative, interesting approach, says HIV researcher Carrie Dykes, PhD, of the University of Rochester, New York. Dykes was not involved in the Dadachova/Goldstein study.
"I think it could play out," Dykes tells WebMD. "They have a lot of animal studies to do before they get into humans. But it would be interesting to see if it would really work."
Current therapy for HIV -- known as highly active antiretroviral therapy or HAART -- uses a combination of powerful drugs that keep the AIDS virus from replicating. When treatment is successful, the virus seems to disappear from the blood.
But once treatment stops, the virus eventually comes back. That's because HIV hides in a few long-lived cells -- so-called latent HIV infection.
If a person gets HAART treatment very, very soon after infection, it's possible to stop the virus before it can establish hideouts. But there is a very narrow window of opportunity to begin this treatment -- as little as a day, and certainly within 72 hours of exposure.
That's because HAART has to work before it starts to replicate within cells. But if radioimmunotherapy were available, the treatment could seek out infected cells and kill them -- effectively widening the window of opportunity to eliminate HIV infection.
Moreover, new strategies are being developed to flush HIV out of hiding. Such strategies, combined with radioimmunotherapy and HAART, might conceivably eradicate HIV, even in established infection. But that hope lies far in the future.
Dykes notes that the researchers haven't yet shown that radioimmunotherapy can track down HIV anywhere in the body. She notes that in the current study, the treatment hit HIV only in liver, spleen, and thymus cells.
"It will be interesting to see whether you could get the radioimmunotherapy to target all the different areas that HIV gets to in the body," she says. "I have a feeling this treatment probably wouldn't cross the blood/brain barrier and get to HIV in the brain."
Dykes agrees with Goldstein that a major benefit of radioimmunotherapy would be to help people for whom HAART simply doesn't work very well.
"A lot of patients out there don't have a lot of treatment options left," Dykes says. "For those patients, this treatment -- which, after all, involves radiation -- might be something they would be willing to do."
"While two-thirds of people with HIV respond well to HAART, others don't," Goldstein says. "If we treat them with radioimmunotherapy to reduce the number of infected cells, we may be able to take patients who are not responsive and make them responsive to HAART."
Dadachova, Goldstein, and colleagues report their findings in the November issue of the open-access, online journal PLOS Medicine.
By Daniel J. DeNoon, reviewed by Louise Chang, MD
SOURCES: Dadachova, E. PLOS Medicine, November 2006; vol 3: pp e427. Ekaterina Dadachova, PhD, Albert Einstein College of Medicine, New York. Harris Goldstein, MD, director, Einstein/MMC Center for AIDS Research, New York. Carrie Dykes, PhD, University of Rochester, New York.