3 years ago

Fc-mediated Anomalous Biodistribution of Therapeutic Antibodies in Immunodeficient Mouse Models.

Dalya Abdel-Atti, Delphine Vivier, J T Poirier, Sebastien Monette, Jason S Lewis, Thomas R Dilling, Brian M Zeglis, Andrew Chow, Jacob Pourat, Kimberly J Edwards, Sai Kiran Sharma
A critical benchmark in the development of antibody-based therapeutics is demonstration of efficacy in preclinical mouse models of human disease, many of which rely on immunodeficient mice. However, relatively little is known about how the biology of various immunodeficient strains impacts the in vivo fate of these drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric and murine monoclonal antibodies against four therapeutic oncologic targets to interrogate their biodistribution in four different strains of immunodeficient mice bearing lung, prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse host as well as both the biological origin and glycosylation of the antibody contributed significantly to the anomalous biodistribution of therapeutic monoclonal antibodies in an Fc receptor-dependent manner. These findings may have important implications for the preclinical evaluation of Fc-containing therapeutics and highlight a clear need for biodistribution studies in the early stages of antibody drug development.

Publisher URL: http://doi.org/10.1158/0008-5472.CAN-17-1958

DOI: 10.1158/0008-5472.CAN-17-1958

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