Fc-mediated anomalous biodistribution of therapeutic antibodies in immunodeficient mouse models Academic Article uri icon

Overview

MeSH Major

  • Autoimmunity
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Central Nervous System
  • Paraneoplastic Syndromes, Nervous System

abstract

  • © 2018 American Association for Cancer Research. 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.

publication date

  • April 2018

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5882577

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-17-1958

PubMed ID

  • 29363548

Additional Document Info

start page

  • 1820

end page

  • 1832

volume

  • 78

number

  • 7