Radioimmunotherapy of Blastomycosis in a Mouse Model With a (1→3)-β-Glucans Targeting Antibody.

Invasive fungal infections (IFI) cause devastating morbidity and mortality, with the number of IFIs more than tripling since 1979. Our laboratories were the first to demonstrate that radiolabeled microorganism-specific monoclonal antibodies are highly effective for treatment of experimental fungal, bacterial and viral infections. Later we proposed to utilize surface expressed pan-antigens shared by major IFI-causing pathogens such as beta-glucans as RIT targets. Here we evaluated RIT targeting beta-glucan in which causes serious infections in immunocompromised and immunocompetent individuals and in companion dogs. cells were treated with the 400-2 antibody to (1→3)-β-glucans radiolabeled with the beta-emitter 177Lutetium (Lu) and alpha-emitter 213Bismuth (Bi) and the efficacy of cell kill was determined by colony forming units (CFUs). To determine the antigen-specific localization of the 400-2 antibody , C57BL6 mice were infected intratracheally with 2 × 10 cells and given In-400-2 antibody 24 h later. To evaluate the killing of cells with RIT, intratracheally infected mice were treated with 150 μCi Bi-400-2 and their lungs analyzed for CFUs 96 h post-infection. Bi-400-2 proved to be more effective in killing cells than Lu-400-2. Three times more In-400-2 accumulated in the lungs of infected mice, than in the non-infected ones. Bi-400-2 lowered the fungal burden in the lungs of infected mice more than 2 logs in comparison with non-treated infected controls. In conclusion, our results demonstrate the ability of an anti-(1-3)-beta-D-glucan antibody armed with an alpha-emitter Bi to selectively kill cells and . These first results of the effectiveness of RIT targeting pan-antigens on fungal pathogens warrant further investigation.