Dr. Roffler, Steve R. 's publons link picture

Dr. Roffler, Steve R.

Distinguished Research Fellow
Division Chief
  • 02-2652-3079 (Lab) (Room No: N233)
  • 02-2782-9142 (Fax)

  1. Antibody Engineering
  2. Directed Molecular Evolution
  3. Prodrugs

Education and Positions:
  • Ph.D. University of California, Berkeley

Highlight Detail

Impact of anti-PEG antibody affinity on accelerated blood clearance of pegylated epoetin beta in mice

Dr. Roffler, Steve R.
Biomedicine & Pharmacotherapy, Dec 06, 2021



Antibodies that bind polyethylene glycol (PEG) can be induced by pegylated biomolecules and also exist in a significant fraction of healthy individuals who have never received pegylated medicines. The binding affinity of antibodies against PEG (anti-PEG antibodies) likely varies depending on if they are induced or naturally occurring. Anti-PEG antibodies can accelerate the clearance of pegylated medicines from the circulation, resulting in loss of drug efficacy, but it is unknown how accelerated blood clearance is affected by anti-PEG antibody affinity. We identified a panel of anti-PEG IgG and IgM antibodies with binding avidities ranging over several orders of magnitude to methoxy polyethylene glycol-epoetin beta (PEG-EPO), which is used to treat patients suffering from anemia. Formation of in vitro immune complexes between PEG-EPO and anti-PEG IgG or IgM antibodies was more obvious as antibody affinity increased. Likewise, high affinity anti-PEG antibodies produced greater accelerated blood clearance of PEG-EPO as compared to low affinity antibodies. The molar ratio of anti-PEG antibody to PEG-EPO that accelerates drug clearance in mice correlates with antibody binding avidity. Our study indicates that the bioactivity of PEG-EPO may be reduced due to rapid clearance in patients with either high concentrations of low affinity or low concentrations of high affinity anti-PEG IgG and IgM antibodies.