Reuters Health Information (2006-11-13): Radiolabeled antibodies kill HIV-1-infected cells
Drug & Device Development
Radiolabeled antibodies kill HIV-1-infected cells
Last Updated: 2006-11-13 19:25:44 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Radiolabeling antibodies to HIV proteins may provide a successful strategy against the infection, investigators in Germany and the US report in the November issue of PLoS Medicine.
An antibody to HIV-1 envelope glycoprotein 41 tagged with the radioisotope rhenium-188 kills cultured white blood cells either chronically or acutely infected with HIV-1, report Ekaterina Dadachova, of the Albert Einstein College of Medicine in Bronx, New York, and her colleagues. The same agent selectively kills HIV-1-infected cells in two mouse models of human infection, without causing acute hematologic toxicity.
"We envision that the availability of radioimmunotherapy could provide a novel treatment option that may hasten the day when curative regimens are available for the eradication of HIV-1 infections," the team writes.
A similar strategy is already used to treat some cancers, note the researchers. Her group also has demonstrated that radioimmunotherapy can treat fungal and bacterial infections by targeting the microbes themselves.
Now they suggest that this tactic would be even more effective in treating HIV-1 infection, because "the majority of long-lived infected cellular targets are lymphocytes, which are among the most radiosensitive cells in the body." Moreover, this type of treatment may be particularly beneficial for eliminating persistent reservoirs of infected cells.
Their most successful candidate was an antibody to the HIV-1 envelope transmembrane protein gp41, labeled with the radioisotope rhenium-188. In vitro treatment led to the killing of chronically infected human T cells and acutely infected human peripheral blood mononuclear cells.
To test the labeled antibody in vivo, the research team used severe combined immunodeficiency (SCID) mice harboring HIV-1 infected mononuclear cells in their spleens. One hour after infection, the researchers injected their concoction.
By increasing the dose, the authors were able to almost completely eliminate the HIV-1-infected cells. The radiolabeled antibody was also effective in a mouse model of an infected human thymus.
Only at the highest dose was there a nonsignificant decrease in platelet count, which recovered by day 15. The researchers attribute this lack of hematologic toxicity to the specific targeting of HIV-1-infected cells. Unlike tumor cells, they write, "cells expressing microbial antigens are antigenically very different from host tissues and thus provide the potential for exquisite specificity and low-cross-reactivity."
Dr. Dadachova and her associates suggest that radioimmunotherapy would be effective immediately after HIV exposure or for infections caused by multi-drug resistant HIV-1. They add that combination therapy with HAART, or "a cocktail of monoclonal antibodies to various epitopes on the HIV-1 envelope may be desirable."
In a press release from the Albert Einstein College of Medicine, senior author Dr. Arturo Casadevall remarks that "this work introduces a new approach for treating many viral infections, from hepatitis C to Ebola."
PLoS Medicine 2006;3:e427.