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

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.

SUBMITTER: Bailey-Kellogg C

PROVIDER: S-EPMC4282101 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Bailey-Kellogg Chris C Gutiérrez Andres H AH Moise Leonard L Terry Frances F Martin William D WD De Groot Anne S AS

Biotechnology and bioengineering 20140714 11

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 ...[more]

PMID: 24888712

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Project description:BACKGROUND:Alcohol use is a major public health concern associated with an increased risk of morbidity and mortality. Health professionals in primary care commonly see patients with a range of alcohol-related risks and problems, providing an ideal opportunity for screening and brief intervention (BI). OBJECTIVE:This study aimed to develop a prototype for a Web-based tool for use by primary care health professionals (eg, doctors and nurses) to communicate alcohol harm risk to their patients and to engage with them regarding ways this risk could be reduced. METHODS:Following conceptualization and development of prototype wireframes, formative work and pretesting were undertaken. For the formative work, focus groups and key informant interviews were conducted with potential end users of the risk communication tool, including health professionals and consumers. The focus groups and interviews explored perceptions of alcohol risk communication and obtained feedback on the initial prototype. For pretesting, participants (primary care doctors and nurses) completed a Web-based survey followed by a period of pretesting before completion of a follow-up survey. The study was designed to gain feedback on the tool's performance in real-world settings as well as its relevance, ease of use, and any suggested refinements. RESULTS:In the formative work stage, 11 key informants and 7 consumers participated in either focus groups or individual interviews. Participants were very positive about the prototype and believed that it would be useful and acceptable in practice. Key informants identified that the key point of difference with the tool was that it provided all the pieces in 1 place (ie, assessment, interpretation, and resources to support change). Participants provided feedback on how the tool could be improved, and these suggestions were incorporated into the prototype where possible. In the pretesting stage, 7 people (5 doctors and 2 primary care nurses) completed the pretesting. Participants reported that the tool provided a useful framework for an intervention, that it would be acceptable to patients, that it was easy to use, that they would be likely to use it in practice, and that there were no technical issues. CONCLUSIONS:The alcohol risk communication tool was found to be acceptable and has the potential to increase the confidence of health professionals in assessing risk and providing BI.

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Dataset Information

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

Publications

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

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