Using a new strategy featuring radioactive antibodies, researchers at the Albert Einstein College of Medicine of Yeshiva University in Bronx, New York, have successfully targeted and destroyed HIV-infected CD4 cells in laboratory experiments involving mice.

“This study supports the idea that radiation might help in treating people infected with HIV,” says Dr. Arturo Casadevall, Chair of the Department of Microbiology and Immunology and a senior author of the study, which appears in the November issue of the online journal PloS Medicine. “More broadly, this work introduces a new approach for treating the many viral infections, from hepatitis C to Ebola, in which viral proteins are expressed on the surface of infected cells.”

The Einstein researchers used a technique called radioimmunotherapy, in which radioactive molecules (radioisotopes) are piggy-backed onto antibodies. Once injected into the body, the antibodies seek out specific proteins and the radioisotopes destroy the cells to which the protein is attached.

Radioimmunotherapy is an accepted treatment for several types of cancer, including non-Hodgkin’s lymphoma. But at Einstein, investigators have been looking at the possibility of using it to treat various infectious diseases.

In a series of animal studies beginning in 2001, the Einstein researchers have successfully used radioimmunotherapy against a variety of disease-causing infections, including those responsible for cryptococcal meningitis and bacterial pneumonia. With these infections, radioimmunotherapy is used to directly target the disease-causing microorganisms. In the case of HIV, the treatment is used to target HIV-infected CD4 (T4) cells in the body.

In this study, antibodies targeting gp41 – one of HIV’s proteins that can be found on the surface of CD4 cells the virus has infected -- were used. The researchers tagged these antibodies with two different radioisotopes, bismuth 213 and rhenium 188.

To test the therapy, the researchers first injected HIV-infected CD4 cells into the spleens of immune-deficient mice. One hour later, the mice were injected with the radioactive antibodies.

Three days after treatment, the researchers measured the number of HIV-infected cells in the spleens. Compared with control mice treated with antibodies without radioisotopes, the number of HIV-infected CD4 cells in the treated mice was significantly reduced.

“Today’s antiretroviral drug therapies can inhibit the multiplication of HIV and help prevent HIV from infecting additional cells,” says Dr. Harris Goldstein, Director of the Center for AIDS Research at Einstein. “But we currently have no way of eliminating the HIV-infected cells that make these infections chronic. The novelty of this technique is that it targets the cells infected by HIV, which act as ‘factories’ for making more of the virus. So if we could eradicate all the HIV-infected cells in a patient – which would likely require a combination of therapies – then we could start to think about curing HIV-infected patients.”

Dr. Goldstein, also a senior author of the study, notes that radioimmunotherapy might be particularly useful for people newly exposed to HIV. “Studies show that giving [HIV treatment] to people within 24 hours of exposure to HIV can prevent infection from developing,” he says. “But if several days have passed, the virus is able to infect enough cells to cause a chronic HIV infection. By combining standard treatment with radioimmunotherapy, we may be able to prevent lifelong infection in these people by eliminating those initially infected cells.”

Clinical trials using radioimmunotherapy for treating HIV infection are now being planned.