Beyond viability: Advancing CHO cell culture process strategies to modulate host cell protein levels

IF 4.5 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS New biotechnology Pub Date : 2024-10-29 DOI:10.1016/j.nbt.2024.10.003
Ansuman Sahoo, Kyle Devenney, Marcus-Allen Nicolas, Nicholas Zill, Balrina Gupta, Sri Ranganayaki Madabhushi
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Abstract

Chinese Hamster Ovary (CHO) cells are widely utilized in bioprocessing industry for monoclonal antibody (mAb) production. In many instances, challenges persist in achieving sufficient clearance of Host Cell Proteins (HCPs) in the final drug substance. While purification strategies usually offer substantial HCP clearance, certain "problematic" HCPs, particularly lipases, continue to pose significant challenges. This study investigates the accumulation of various "problematic" HCPs in CHO cell culture using transcriptomics, revealing correations between cell culture parameters and HCP level. Contrary to conventional assumptions, viability alone does not reliably predict HCP levels, with factors such as clone selection, host cell line choice, media and feed compositions significantly influencing HCP accumulation. Leveraging transcriptomics-based approaches, we demonstrate the potential of upstream process control strategies to mitigate HCP presence and improve biologic product quality. Our findings underscore the importance of considering diverse cell culture parameters in bioprocess optimization to ensure product stability and quality. While promising, further research is needed to elucidate the mechanisms underlying HCP release and propagation through downstream processing stages, emphasizing the necessity of a comprehensive integrated approach to HCP control in biologics production.
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超越活力:推进 CHO 细胞培养过程策略,调节宿主细胞蛋白质水平。
中国仓鼠卵巢(CHO)细胞被广泛应用于单克隆抗体(mAb)生产的生物加工行业。在许多情况下,要充分清除最终药物物质中的宿主细胞蛋白(HCP)一直是个难题。虽然纯化策略通常能大量清除 HCP,但某些有问题的 HCP,尤其是脂肪酶,却带来了巨大的挑战。本研究利用转录组学研究了各种问题 HCP 在 CHO 细胞培养过程中的积累情况,揭示了细胞培养参数与 HCP 活性之间的相关性。与传统假设相反,单凭活力并不能可靠地预测 HCP 水平,克隆选择、宿主细胞系选择和培养基饲料类型等因素都会对 HCP 的积累产生重大影响。利用基于转录组学的方法,我们展示了上游过程控制策略在减少 HCP 存在和提高生物产品质量方面的潜力。我们的发现强调了在生物工艺优化过程中考虑各种细胞培养参数以确保产品稳定性和质量的重要性。虽然前景广阔,但还需要进一步研究来阐明 HCP 释放和在下游加工阶段传播的机制,强调在生物制品生产中采用全面综合方法控制 HCP 的必要性。
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来源期刊
New biotechnology
New biotechnology 生物-生化研究方法
CiteScore
11.40
自引率
1.90%
发文量
77
审稿时长
1 months
期刊介绍: New Biotechnology is the official journal of the European Federation of Biotechnology (EFB) and is published bimonthly. It covers both the science of biotechnology and its surrounding political, business and financial milieu. The journal publishes peer-reviewed basic research papers, authoritative reviews, feature articles and opinions in all areas of biotechnology. It reflects the full diversity of current biotechnology science, particularly those advances in research and practice that open opportunities for exploitation of knowledge, commercially or otherwise, together with news, discussion and comment on broader issues of general interest and concern. The outlook is fully international. The scope of the journal includes the research, industrial and commercial aspects of biotechnology, in areas such as: Healthcare and Pharmaceuticals; Food and Agriculture; Biofuels; Genetic Engineering and Molecular Biology; Genomics and Synthetic Biology; Nanotechnology; Environment and Biodiversity; Biocatalysis; Bioremediation; Process engineering.
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