Bioinformatic analysis of Chinese hamster ovary host cell protein lipases

MacDonald, Madolyn L.; Hamaker, Nathaniel K.; Lee, Kelvin H.

doi:10.1002/aic.16378

Cited by 6 publications

(2 citation statements)

References 53 publications

(91 reference statements)

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“…Therefore, a reduction in HCPs to minimal levels is required. While most HCPs are removed during downstream purification steps, certain ‘difficult-to-remove’ HCPs often remain ( 62 ). Additionally, stable transfection of mammalian cells is time-consuming, transient transfection has been used to produce VLPs in several studies.…”

Section: Recombinant Dna Technology Applied To Different Host Systems...mentioning

confidence: 99%

Platforms, advances, and technical challenges in virus-like particles-based vaccines

et al. 2023

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Viral infectious diseases threaten human health and global stability. Several vaccine platforms, such as DNA, mRNA, recombinant viral vectors, and virus-like particle-based vaccines have been developed to counter these viral infectious diseases. Virus-like particles (VLP) are considered real, present, licensed and successful vaccines against prevalent and emergent diseases due to their non-infectious nature, structural similarity with viruses, and high immunogenicity. However, only a few VLP-based vaccines have been commercialized, and the others are either in the clinical or preclinical phases. Notably, despite success in the preclinical phase, many vaccines are still struggling with small-scale fundamental research owing to technical difficulties. Successful production of VLP-based vaccines on a commercial scale requires a suitable platform and culture mode for large-scale production, optimization of transduction-related parameters, upstream and downstream processing, and monitoring of product quality at each step. In this review article, we focus on the advantages and disadvantages of various VLP-producing platforms, recent advances and technical challenges in VLP production, and the current status of VLP-based vaccine candidates at commercial, preclinical, and clinical levels.

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Section: Recombinant Dna Technology Applied To Different Host Systems...mentioning

confidence: 99%

Platforms, advances, and technical challenges in virus-like particles-based vaccines

et al. 2023

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“…In addition, there could be other HCPs that potentially possess the lipase activities that contribute to the degradation of polysorbates, but their functions are yet to be identified or confirmed. 13 These lipase HCPs are found to often co-purify with many monoclonal antibodies (mAbs) and other biotherapeutics produced in Chinese hamster ovary (CHO) cells. 14,15 As a result, they can affect drug substance stability and need to be removed from the drug substance to acceptable levels.…”

Section: Introductionmentioning

confidence: 99%

A Highly Sensitive LC-MS/MS Method for Targeted Quantitation of Lipase Host Cell Proteins in Biotherapeutics

Chen

Stanley

et al. 2021

Journal of Pharmaceutical Sciences

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Identification and accurate quantitation of host cell proteins (HCPs) in biotherapeutic drugs has become increasingly important due to the negative impact of certain HCPs on the safety, stability, and other product quality of biotherapeutics. Recently, several lipase HCPs have been identified to potentially cause the enzymatic degradation of polysorbate, a widely used excipient in the formulation of biotherapeutics, which can severely impact the stability and product quality of drug products. In this study, we identified three lipase HCPs that were frequently detected in Chinese hamster ovary (CHO) cell cultures using shotgun proteomics, including phospholipase B-like 2 (PLBL2), lipoprotein lipase (LPL), and lysosomal acid lipase (LIPA). A targeted quantitation method for these three lipase HCPs was developed utilizing liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) with high-resolution multiple-reaction-monitoring (MRMhr) quantitation. The method demonstrated good sensitivity with low limit of quantitation (LLOQ) around 1 ng/mL, and linear dynamic range of three orders of magnitude for the three lipase HCPs. It has been applied for the characterization of process intermediates from various in-house monoclonal antibody (mAb) production. In addition, the method has also been used to evaluate the robustness of clearance for one of the lipase HCPs, PLBL2, under different column purification process conditions.

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