✦ LIBER ✦

Glass particles as an adjuvant: A model for adverse immunogenicity of therapeutic proteins

✍ Scribed by Amber Haynes Fradkin; John F. Carpenter; Theodore W. Randolph

Publisher: John Wiley and Sons
Year: 2011
Tongue: English
Weight: 334 KB
Volume: 100
Category: Article
ISSN: 0022-3549
DOI: 10.1002/jps.22683

No coin nor oath required. For personal study only.

✦ Synopsis

Unwanted immune responses to parenterally administered therapeutic proteins pose serious safety and economic risks, but the mechanism(s) by which these responses are generated are unknown. We measured immune responses to aggregates of recombinant murine growth hormone (mGH) formed by agitation or freeze-thawing, two pharmaceutically relevant stresses, as well as to mGH adsorbed on microscopic glass or alum particles. Insoluble aggregates, even at levels below the detection limits of size-exclusion high-performance liquid chromatography analysis (<1%), induce immune responses when administered subcutaneously. Furthermore, we show that application of high hydrostatic pressures (200 MPa) reduces aggregate levels to 0.02 ng/dose and eliminates immunogenicity.

📜 SIMILAR VOLUMES

An industry perspective on the monitorin

An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics

✍ Satish K. Singh; Nataliya Afonina; Michel Awwad; Karoline Bechtold-Peters; Jeffr 📂 Article 📅 2010 🏛 John Wiley and Sons 🌐 English ⚖ 399 KB 👁 1 views

Concern around the lack of monitoring of proteinaceous subvisible particulates in the 0.1-10 mm range has been heightened (Carpenter et al., 2009, J Pharm Sci 98: 1202-1205), primarily due to uncertainty around the potential immunogenicity risk from these particles. This article, representing the op