Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers.

Publication ,  Journal Article
Moreno, A; Pitoc, GA; Ganson, NJ; Layzer, JM; Hershfield, MS; Tarantal, AF; Sullenger, BA
Published in: Cell Chem Biol
May 16, 2019

Biopharmaceuticals have become increasingly attractive therapeutic agents and are often PEGylated to enhance their pharmacokinetics and reduce their immunogenicity. However, recent human clinical trials have demonstrated that administration of PEGylated compounds can evoke anti-PEG antibodies. Considering the ubiquity of PEG in commercial products and the presence of pre-existing anti-PEG antibodies in patients in large clinical trials evaluating a PEG-modified aptamer, we investigated how anti-PEG antibodies effect the therapeutic activities of PEGylated RNA aptamers. We demonstrate that anti-PEG antibodies can directly bind to and inhibit anticoagulant aptamer function in vitro and in vivo. Moreover, in parallel studies we detected the presence of anti-PEG antibodies in nonhuman primates after a single administration of a PEGylated aptamer. Our results suggest that anti-PEG antibodies can limit the activity of PEGylated drugs and potentially compromise the activity of otherwise effective therapeutic agents.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cell Chem Biol

DOI

EISSN

2451-9448

Publication Date

May 16, 2019

Volume

26

Issue

5

Start / End Page

634 / 644.e3

Location

United States

Related Subject Headings

  • Thrombosis
  • Polyethylene Glycols
  • Partial Thromboplastin Time
  • Mice, Inbred C57BL
  • Mice
  • Macaca mulatta
  • Humans
  • Ferric Compounds
  • Female
  • Factor IXa
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Moreno, A., Pitoc, G. A., Ganson, N. J., Layzer, J. M., Hershfield, M. S., Tarantal, A. F., & Sullenger, B. A. (2019). Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers. Cell Chem Biol, 26(5), 634-644.e3. https://doi.org/10.1016/j.chembiol.2019.02.001
Moreno, Angelo, George A. Pitoc, Nancy J. Ganson, Juliana M. Layzer, Michael S. Hershfield, Alice F. Tarantal, and Bruce A. Sullenger. “Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers.Cell Chem Biol 26, no. 5 (May 16, 2019): 634-644.e3. https://doi.org/10.1016/j.chembiol.2019.02.001.
Moreno A, Pitoc GA, Ganson NJ, Layzer JM, Hershfield MS, Tarantal AF, et al. Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers. Cell Chem Biol. 2019 May 16;26(5):634-644.e3.
Moreno, Angelo, et al. “Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers.Cell Chem Biol, vol. 26, no. 5, May 2019, pp. 634-644.e3. Pubmed, doi:10.1016/j.chembiol.2019.02.001.
Moreno A, Pitoc GA, Ganson NJ, Layzer JM, Hershfield MS, Tarantal AF, Sullenger BA. Anti-PEG Antibodies Inhibit the Anticoagulant Activity of PEGylated Aptamers. Cell Chem Biol. 2019 May 16;26(5):634-644.e3.

Published In

Cell Chem Biol

DOI

EISSN

2451-9448

Publication Date

May 16, 2019

Volume

26

Issue

5

Start / End Page

634 / 644.e3

Location

United States

Related Subject Headings

  • Thrombosis
  • Polyethylene Glycols
  • Partial Thromboplastin Time
  • Mice, Inbred C57BL
  • Mice
  • Macaca mulatta
  • Humans
  • Ferric Compounds
  • Female
  • Factor IXa