Radioimmunotherapy shows promise for HIV, viral cancer treatments
Scientists at Albert Einstein College of Medicine of Yeshiva University in New York City have piggybacked antibodies onto radioactive payloads to deliver radiation dosages that selectively target and destroy microbial and HIV-infected cells.
The treatment--called radioimmunotherapy (RIT)--holds promise for treating various infectious diseases, including HIV and cancers caused by viruses, according to research presented Feb. 14 at the annual meeting of the American Association for the Advancement of Science (AAAS) in New York City.
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, 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, according to presenter Ekaterina Dadachova, PhD, a RIT researcher and an associate professor of nuclear medicine and of microbiology and immunology at Einstein.
Devising RIT for HIV posed significant challenges, since viruses are tiny bits of DNA or RNA wrapped in a thin protein coat that can easily shrug off radiation directed at them and 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," Dadachova said. "Fortunately, lymphocytes are among the most radiosensitive cells in the body."
The researchers used RIT consisting of an antibody for glycoprotein 41 (gp41) and the radioactive isotope 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 radioactive-labeled antibodies to miss their target. Bismuth-213 was chosen because of several characteristics, including a half-life 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.
Dadachova and colleagues demonstrated that the treatment can effectively eliminate HIV-infected human cells in both laboratory and animal studies, the latter involving two different models of mice with HIV. 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.
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 metastatic disease.
"Many virus-associated cancer cells continue to express viral antigens," Dadachova explained. "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."
The treatment--called radioimmunotherapy (RIT)--holds promise for treating various infectious diseases, including HIV and cancers caused by viruses, according to research presented Feb. 14 at the annual meeting of the American Association for the Advancement of Science (AAAS) in New York City.
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, 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, according to presenter Ekaterina Dadachova, PhD, a RIT researcher and an associate professor of nuclear medicine and of microbiology and immunology at Einstein.
Devising RIT for HIV posed significant challenges, since viruses are tiny bits of DNA or RNA wrapped in a thin protein coat that can easily shrug off radiation directed at them and 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," Dadachova said. "Fortunately, lymphocytes are among the most radiosensitive cells in the body."
The researchers used RIT consisting of an antibody for glycoprotein 41 (gp41) and the radioactive isotope 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 radioactive-labeled antibodies to miss their target. Bismuth-213 was chosen because of several characteristics, including a half-life 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.
Dadachova and colleagues demonstrated that the treatment can effectively eliminate HIV-infected human cells in both laboratory and animal studies, the latter involving two different models of mice with HIV. 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.
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 metastatic disease.
"Many virus-associated cancer cells continue to express viral antigens," Dadachova explained. "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."