Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biotechnol Bioeng. 2014 Nov;111(11):2170-82. doi: 10.1002/bit.25286. Epub 2014 Jul 14.

CHOPPI: a web tool for the analysis of immunogenicity risk from host cell proteins in CHO-based protein production.

Author information

  • 1Department of Computer Science, Dartmouth College, Hanover, New Hampshire.

Abstract

Despite high quality standards and continual process improvements in manufacturing, host cell protein (HCP) process impurities remain a substantial risk for biological products. Even at low levels, residual HCPs can induce a detrimental immune response compromising the safety and efficacy of a biologic. Consequently, advanced-stage clinical trials have been cancelled due to the identification of antibodies against HCPs. To enable earlier and rapid assessment of the risks in Chinese Hamster Ovary (CHO)-based protein production of residual CHO protein impurities (CHOPs), we have developed a web tool called CHOPPI, for CHO Protein Predicted Immunogenicity. CHOPPI integrates information regarding the possible presence of CHOPs (expression and secretion) with characterizations of their immunogenicity (T cell epitope count and density, and relative conservation with human counterparts). CHOPPI can generate a report for a specified CHO protein (e.g., identified from proteomics or immunoassays) or characterize an entire specified subset of the CHO genome (e.g., filtered based on confidence in transcription and similarity to human proteins). The ability to analyze potential CHOPs at a genomic scale provides a baseline to evaluate relative risk. We show here that CHOPPI can identify clear differences in immunogenicity risk among previously validated CHOPs, as well as identify additional "risky" CHO proteins that may be expressed during production and induce a detrimental immune response upon delivery. We conclude that CHOPPI is a powerful tool that provides a valuable computational complement to existing experimental approaches for CHOP risk assessment and can focus experimental efforts in the most important directions. Biotechnol. Bioeng. 2014;111: 2170-2182. © 2014 Wiley Periodicals, Inc.

© 2014 Wiley Periodicals, Inc.

KEYWORDS:

CHO; T cell epitope; biologic; host cell protein; immunogenicity; immunoinformatics

PMID:
24888712
[PubMed - indexed for MEDLINE]
PMCID:
PMC4282101
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Write to the Help Desk