PlumX Metrics
Embed PlumX Metrics

Engineered Monoclonal Antibody with Novel Antigen-Sweeping Activity In Vivo

PLoS ONE, ISSN: 1932-6203, Vol: 8, Issue: 5, Page: e63236
2013
  • 91
    Citations
  • 0
    Usage
  • 143
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

Monoclonal antibodies are widely used to target disease-related antigens. However, because conventional antibody binds to the antigen but cannot eliminate the antigen from plasma, and rather increases the plasma antigen concentration by reducing the clearance of the antigen, some clinically important antigens are still difficult to target with monoclonal antibodies because of the huge dosages required. While conventional antibody can only bind to the antigen, some natural endocytic receptors not only bind to the ligands but also continuously eliminate them from plasma by pH-dependent dissociation of the ligands within the acidic endosome and subsequent receptor recycling to the cell surface. Here, we demonstrate that an engineered antibody, named sweeping antibody, having both pH-dependent antigen binding (to mimic the receptor-ligand interaction) and increased binding to cell surface neonatal Fc receptor (FcRn) at neutral pH (to mimic the cell-bound form of the receptor), selectively eliminated the antigen from plasma. With this novel antigen-sweeping activity, antibody without in vitro neutralizing activity exerted in vivo efficacy by directly eliminating the antigen from plasma. Moreover, conversion of conventional antibody with in vitro neutralizing activity into sweeping antibody further potentiated the in vivo efficacy. Depending on the binding affinity to FcRn at neutral pH, sweeping antibody reduced antigen concentration 50- to 1000-fold compared to conventional antibody. Thereby, sweeping antibody antagonized excess amounts of antigen in plasma against which conventional antibody was completely ineffective, and could afford marked reduction of dosage to a level that conventional antibody can never achieve. Thus, the novel mode of action of sweeping antibody provides potential advantages over conventional antibody and may allow access to the target antigens which were previously undruggable by conventional antibody. © 2013 Igawa et al.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84877147797&origin=inward; http://dx.doi.org/10.1371/journal.pone.0063236; http://www.ncbi.nlm.nih.gov/pubmed/23667591; https://dx.plos.org/10.1371/journal.pone.0063236.g001; http://dx.doi.org/10.1371/journal.pone.0063236.g001; https://dx.plos.org/10.1371/journal.pone.0063236.g002; http://dx.doi.org/10.1371/journal.pone.0063236.g002; https://dx.plos.org/10.1371/journal.pone.0063236.g004; http://dx.doi.org/10.1371/journal.pone.0063236.g004; https://dx.plos.org/10.1371/journal.pone.0063236.g005; http://dx.doi.org/10.1371/journal.pone.0063236.g005; https://dx.plos.org/10.1371/journal.pone.0063236; https://dx.plos.org/10.1371/journal.pone.0063236.g003; http://dx.doi.org/10.1371/journal.pone.0063236.g003; https://dx.plos.org/10.1371/journal.pone.0063236.t001; http://dx.doi.org/10.1371/journal.pone.0063236.t001; https://dx.doi.org/10.1371/journal.pone.0063236.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0063236.g001; https://dx.doi.org/10.1371/journal.pone.0063236.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0063236.g003; https://dx.doi.org/10.1371/journal.pone.0063236.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0063236.g004; https://dx.doi.org/10.1371/journal.pone.0063236.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0063236.g002; https://dx.doi.org/10.1371/journal.pone.0063236.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0063236.g005; https://dx.doi.org/10.1371/journal.pone.0063236.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0063236.t001; https://dx.doi.org/10.1371/journal.pone.0063236; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063236; http://dx.plos.org/10.1371/journal.pone.0063236.t001; http://dx.plos.org/10.1371/journal.pone.0063236; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063236&type=printable; http://dx.plos.org/10.1371/journal.pone.0063236.g003; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0063236; http://dx.plos.org/10.1371/journal.pone.0063236.g001; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0063236; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0063236&type=printable; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063236; http://dx.plos.org/10.1371/journal.pone.0063236.g004; http://dx.plos.org/10.1371/journal.pone.0063236.g002; http://dx.plos.org/10.1371/journal.pone.0063236.g005

Tomoyuki Igawa; Atsuhiko Maeda; Kenta Haraya; Tatsuhiko Tachibana; Yuki Iwayanagi; Futa Mimoto; Yoshinobu Higuchi; Shinya Ishii; Shigero Tamba; Naoka Hironiwa; Kozue Nagano; Tetsuya Wakabayashi; Hiroyuki Tsunoda; Kunihiro Hattori; Maria Gasset

Public Library of Science (PLoS)

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Multidisciplinary

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know