AUTHOR=Helal Muath , Allen Kevin J. H. , van Dijk Bruce , Nosanchuk Joshua D. , Snead Elisabeth , Dadachova Ekaterina 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00147

DOI=10.3389/fmicb.2020.00147

ISSN=1664-302X

ABSTRACT=<p>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 <italic>in vivo</italic> RIT targeting beta-glucan in <italic>Blastomyces dermatitidis</italic> which causes serious infections in immunocompromised and immunocompetent individuals and in companion dogs. <italic>B. dermatitidis</italic> cells were treated with the 400-2 antibody to (1→3)-β-glucans radiolabeled with the beta-emitter 177Lutetium (<sup>177</sup>Lu) and alpha-emitter 213Bismuth (<sup>213</sup>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 <italic>in vivo</italic>, C57BL6 mice were infected intratracheally with 2 × 10<sup>5</sup><italic>B. dermatitidis</italic> cells and given <sup>111</sup>In-400-2 antibody 24 h later. To evaluate the killing of <italic>B. dermatitidis</italic> cells with RIT, intratracheally infected mice were treated with 150 μCi <sup>213</sup>Bi-400-2 and their lungs analyzed for CFUs 96 h post-infection. <sup>213</sup>Bi-400-2 proved to be more effective in killing <italic>B. dermatitidis</italic> cells <italic>in vitro</italic> than <sup>177</sup>Lu-400-2. Three times more <sup>111</sup>In-400-2 accumulated in the lungs of infected mice, than in the non-infected ones. <sup>213</sup>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 <sup>213</sup>Bi to selectively kill <italic>B. dermatitidis</italic> cells <italic>in vitro</italic> and <italic>in vivo</italic>. These first <italic>in vivo</italic> results of the effectiveness of RIT targeting pan-antigens on fungal pathogens warrant further investigation.</p>