Radioactive Antibody "Missiles" Home In on HIV

Taking their cue from cancer therapies, U.S. and German researchers attached radioactive isotopes to HIV-specific antibodies in a proof-of-principle study attempting to show HIV-infected cells can be selectively destroyed during acute or chronic infection. The technique was employed in mice; researchers hope someday the approach can be used in humans.

"Twenty-five years from the start of the epidemic, HIV is still an incurable disease -- something completely different needs to be done to eradicate it," said study co-author Ekaterina Dadachova, a nuclear medicine specialist from the Albert Einstein College of Medicine in New York City.

Dadachova and colleagues hypothesized that radioactive isotopes could be used to cluster around HIV-infected cells, killing them while leaving the rest of cells unharmed. The approach has been successful when targeting certain tumor cells.

The team linked radioisotopes bismuth 213 and rhenium 188 with antibodies to the HIV envelope's glycoproteins 120 and 41 (gp120 and gp41). They then injected the radioactive antibodies into mice engineered to have HIV-infected blood cells.

Treated mice had less than half the infected cells of untreated mice, and the mice suffered cellular damage only at the highest antibody dose, the researchers reported. The investigators are working with a pharmaceutical group to see if clinical trials are warranted.

Particularly, before HIV infection has been fully established and the immune system has responded, the technique could in principal supplement antiretroviral therapy for a brief time, said AIDS vaccine researcher David Montefiori of Duke University.

"This is the type of treatment technology that gives one hope it might be possible to eliminate the virus," said Montefiori, who is unaffiliated with the study. However, as HIV infection progresses, some cells turn dormant and would not cover themselves in the proteins that such antibodies recognize. Treatment or eradication is only possible, he said, "if this therapy is effective in killing HIV-infected cells in humans, as it was in mice, and if the latently infected cells can be induced to express viral antigens. Those are two big if's."

The full open-access report, "Targeted Killing of Virally Infected Cells by Radiolabeled Antibodies to Viral Proteins," was published in Public Library of Science Medicine (2006;3(11):e427 doi:10.1371/journal.pmed.0030427).

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