Yeshiva University scientists claim to have succeeded in piggybacking antibodies onto radioactive payloads so as to deliver doses of radiation that selectively target and destroy microbial and HIV-infected cells.
The researchers hope that the experimental treatment, known as radioimmunotherapy (RIT), may be helpful in treating various infectious diseases, including HIV and cancers caused by viruses.
Dr. Ekaterina Dadachova, of Albert Einstein College of Medicine, says that RIT, which is currently used in cancer treatment, capitalizes on the fact that each type of antibody is programmed to seek out just one type of antigen in the body.
Thus, says the researcher, 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.
While making a presentation at the annual meeting of the American Association for the Advancement of Science (AAAS), the researcher revealed that 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.
Since viruses are quite different from cancer cells, devising radioimmunotherapy for HIV posed significant challenges. 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. Fortunately, lymphocytes are among the most radiosensitive cells in the body," says Dr. Dadachova.
The Einstein researchers have revealed that the RIT they have devised 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.
They said that they selected the gp41 antibody because its corresponding gp41 antigen is reliably expressed on the surface of cells infected with HIV.
Unlike other HIV-related glycoproteins, said the researchers, gp41 antigen usually is not shed into the bloodstream, which would lead many of radioactive-labeled antibodies to miss their target.
The team said that they chose Bismuth-213 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.
Drs. Dadachova and Casadevall showed that the treatment could effectively eliminate HIV-infected human cells in both laboratory and animal studies, the latter involving two different models of mice with HIV.
The researchers are presently carrying out pre-clinical testing of the therapy's efficacy and safety in preparation for a Phase I clinical trial in HIV-infected patients.
According to them, RIT also has potential as a therapy for cancers that are preceded by viral infections, such as cervical cancer (certain forms of which are associated with human papilloma virus) and hepatocellular carcinoma (associated with hepatitis B virus). Such cancers account for almost a quarter of all cancers.
"Many virus-associated cancer cells continue to express viral antigens. As these antigens are not found anywhere else in the body, RIT of viral cancers promises exquisite specificity of treatment and very low toxicity to the patient," Dr. Dadachova says.