Scientists have effectively eliminated HIV infected human cells in both laboratory and animal studies with an experimental treatment called radioimmunotherapy, or RIT. The animal studies involved two different models of mice with HIV.
RIT was originally developed as a therapy for cancer treatment and has been the most successful so far in treatment of non-Hodgkin lymphoma, a cancer that originates in cells of the immune system. RIT allows concentrated radiation at tumor sites, reducing the amount of radiation that reaches healthy tissue.
The researchers piggybacked antibodies onto radioactive payloads to deliver doses of radiation that selectively targeted and destroyed HIV infected cells, making RIT a promising treatment for various infectious diseases, including HIV.
RIT capitalizes on the fact that each type of antibody is programmed to seek out just one type of antigen in the body. Thus, by attaching radioactive material to a particular antibody, radiation can be targeted at specific cells that express the corresponding antigen, minimizing collateral damage to other tissues. This level of specificity is not possible with existing forms of radiation therapy.
Since viruses are quite different from cancer cells and devising radioimmunotherapy for HIV posed significant challenges for the scientists. Viruses are tiny bits of DNA or RNA wrapped in a thin protein coat. Simple, tough, and resilient, viruses easily shrug off radiation directed at them and can readily repair any damage that might occur. Complicating matters, HIV can hide in immune cells keeping the virus beyond the reach of antibodies.
“Our approach is not to target the virus particles themselves, but rather lymphocytes that harbor the virus,” says Dr. Dadachova. “Fortunately, lymphocytes are among the most radiosensitive cells in the body.”
The RIT devised by the researchers consists of an antibody for glycoprotein 41 (gp41) and a radioactive isotope called Bismuth-213, bound together with a special molecule known as a ligand. The gp41 antibody was selected because its corresponding gp41 antigen is reliably expressed on the surface of cells infected with HIV. In addition, unlike other HIV related glycoproteins, gp41 antigen usually is not shed into the bloodstream, which would lead many of radioactive-labeled antibodies to miss their target. Bismuth-213 was chosen because of several characteristics, including a half-life, or decay rate, of 46 minutes. Such a short half-life rate allows just enough time for the treatment to be administered and for the radioactive antibodies to do their job. After four hours, Bismuth-213 radioactivity falls to negligible levels.
The team is now conducting pre-clinical testing of the therapy’s efficacy and safety in preparation for a Phase I clinical trial in HIV infected patients.
References:
1. Dadachova E, Patel MC, Toussi S, Apostolidis C, Morgenstern A, Brechbiel MW, Gorny MK, Zolla-Pazner S, Casadevall A, Goldstein H.. (2006) Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. PLoS Med 3(11): e427.
2. X-G. Wang, E. Revskaya, R A. Bryan, H.D. Strickler, R. D. Burk, A. Casadevall, E. Dadachova (2007) Treating cancer as an infectious disease – viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology. PLOS One 2(10): e1114.
3. Dadachova E, Casadevall A.(2009) Radioimmunotherapy of infectious diseases. Semin Nucl Med. 39(2):146-53.
4. Ekaterina Dadachova, et al. Albert Einstein College of Medicine.
