Fc-mediated anomalous biodistribution of therapeutic antibodies in immunodeficient mouse models Journal Article

Authors: Sharma, S. K.; Chow, A.; Monette, S.; Vivier, D.; Pourat, J.; Edwards, K. J.; Dilling, T. R.; Abdel-Atti, D.; Zeglis, B. M.; Poirier, J. T.; Lewis, J. S.
Article Title: Fc-mediated anomalous biodistribution of therapeutic antibodies in immunodeficient mouse models
Abstract: 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 mAbs 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. Significance: Fc/FcgR-mediated immunobiology of the experimental host is a key determinant to preclinical in vivo tumor targeting and efficacy of therapeutic antibodies. © 2018 American Association for Cancer Research.
Journal Title: Cancer Research
Volume: 78
Issue: 7
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2018-04-01
Start Page: 1820
End Page: 1832
Language: English
DOI: 10.1158/0008-5472.can-17-1958
PROVIDER: scopus
PMCID: PMC5882577
PUBMED: 29363548
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Sebastien Monette
    78 Monette
  2. Brian Zeglis
    69 Zeglis
  3. Jason S Lewis
    267 Lewis
  4. John Thomas Poirier
    66 Poirier
  5. Arthur W Chow
    13 Chow
  6. Sai Kiran   Sharma
    15 Sharma
  7. Kimberly Joanna Edwards
    10 Edwards
  8. Jacob   Pourat
    6 Pourat