HIV Cure Potentially Lies in Radioimmutherapy

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A study was recently presented at the annual meeting of the Radiological Society of North America (RSNA) that observed the use of radioimmunotherapy (RIT) to eradicate residual human immunodeficiency virus (HIV)-infected cells in the blood samples of patients treated with antiretroviral therapy, presenting a promising approach for curing HIV infection.

Highly active antiretroviral therapy (HAART) has altered the stance for patients infected with HIV by suppressing the duplication of the virus in the body. However, despite the success of HAART in successfully decreasing the heavy load of HIV, scientists believe reservoirs of latently infected cells persist in the body, canceling out the possibility of a permanent remedy.

"In an HIV patient on HAART, drugs suppress viral replication, which means they keep the number of viral particles in a patient's bloodstream very low. However, HAART cannot kill the HIV-infected cells. Any strategy for curing HIV infection must include a method to eliminate viral-infected cells,” said professor of radiology, microbiology and immunology at Albert Einstein College of Medicine in the Bronx, N.Y. and the study’s lead author, Ekaterina Dadachova, Ph.D.

For the study, Dadachova and a team of researchers provided RIT to blood samples from 15 HIV patients treated with HAART at the Einstein-Montefiore Center for AIDS Research.

As a matter of fact, from a historical point of view, RIT has been utilized to treat cancer, as it employs monoclonal antibodies, which are cloned cells that are enlisted by the immune system to identify and liquidate antigens. Antigens are foreign objects like bacteria and viruses that provoke an immune response in the body. The antibod


y, designed to recognize and bind to a specific cell antigen, is paired with a radioactive isotope. When injected into the patient's bloodstream, the laboratory-developed antibody travels to the target cell where the radiation is then delivered.

“In RIT, the antibodies bind to the infected cells and kill them by radiation. When HAART and RIT are used together, they kill the virus and the infected cells, respectively,” said Dadachova.

For this study, Dadachova and her research team matched the monoclonal antibody (mAb2556) designed to target a protein exhibited on the surface of HIV-infected cells with the radionuclide Bismuth-213.

The researchers discovered that RIT was able to kill HIV-infected lymphocytes previously treated with HAART, significantly lessening the HIV infection in the blood samples to undetectable levels.

"The elimination of HIV-infected cells with RIT was profound and specific. The radionuclide we used delivered radiation only to HIV-infected cells without damaging nearby cells,” noted Dadachova.

A crucial part of the study tested the ability of the radiolabeled antibody to reach HIV-infected cells in the brain and central nervous system. Using an in vitro human blood brain barrier model, the researchers showed that radiolabeled mAb2556 could make it passed the blood brain barrier and destroy HIV-infected cells without any explicit damage to the barrier itself.

"Antiretroviral treatment only partially penetrates the blood brain barrier, which means that even if a patient is free of HIV systemically, the virus is still able to rage on in the brain, causing cognitive disorders and mental decline. Our study showed that RIT is able to kill HIV-infected cells both systemically and within the central nervous system,” said Dadachova.

Dadachova notes that the next step for the RIT treatment will be performing clinical trials in HIV patients.

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