Biotechnology Progress最新文献_第10页

Catechins prevent monoclonal antibody fragmentation during production via fed-batch culture of Chinese hamster ovary cells 儿茶素可防止中国仓鼠卵巢细胞批量喂养生产过程中出现单克隆抗体碎片。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-28 DOI: 10.1002/btpr.3447

Tsuyoshi Yamaguchi, Hiroko Ishikawa, Mie Fukuda, Yumi Sugita, Misaki Furuie, Ryuma Nagano, Toshiyuki Suzawa, Koichi Yamamoto, Kaori Wakamatsu

{"title":"Catechins prevent monoclonal antibody fragmentation during production via fed-batch culture of Chinese hamster ovary cells","authors":"Tsuyoshi Yamaguchi, Hiroko Ishikawa, Mie Fukuda, Yumi Sugita, Misaki Furuie, Ryuma Nagano, Toshiyuki Suzawa, Koichi Yamamoto, Kaori Wakamatsu","doi":"10.1002/btpr.3447","DOIUrl":"10.1002/btpr.3447","url":null,"abstract":"Chinese hamster ovary (CHO) cells are widely used for the industrial production of therapeutic monoclonal antibodies (mAbs). To meet the increasing market demands, high productivity, and quality are required in cell culture. One of the critical attributes of mAbs, from a safety perspective, is mAb fragmentation. However, methods for preventing mAbs fragmentation in CHO cell culture are limited. In this study, we observed that the antibody fragment content increased with increasing titers in fed-batch cultures for all three cell lines expressing recombinant antibodies. Adding copper sulfate to the culture medium further increased the fragment content, suggesting the involvement of reactive oxygen species (ROS) in the fragmentation process. Though antioxidants may be helpful to scavenge ROS, several antioxidants are reported to decrease the productivity of CHO cells. Among the antioxidants examined, we observed that the addition of catechin or (−)-epigallocatechin gallate to the culture medium prevented fragmentation content by about 20% and increased viable cell density and titer by 30% and 10%, respectively. Thus, the addition of catechins or compounds of equivalent function would be beneficial for manufacturing therapeutic mAbs with a balance between high titers and good quality.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.3447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Application of fucosylation inhibitors for production of afucosylated antibody 应用岩藻糖基化抑制剂生产岩藻糖基化抗体。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-28 DOI: 10.1002/btpr.3438

Ping Xu, Yu Chuan Ou, Michael Smith, Jim Paulson, Michael A. Schmidt, Lakshmi Kandari, Rodney Parsons, Anurag Khetan

引用次数: 0

Biotransformation of maize bran-derived ferulic acid to vanillin using an adapted strain of Amycolatopsis sp. ATCC 39116 利用一株适应的 Amycolatopsis sp. ATCC 39116，将玉米麸皮衍生的阿魏酸生物转化为香兰素。

IF 2.9 3区生物学

Biotechnology Progress Pub Date : 2024-02-28 DOI: 10.1002/btpr.3417

Rasika V. Tupe, Nitesh K. Singh, Annamma A. Odaneth

{"title":"Biotransformation of maize bran-derived ferulic acid to vanillin using an adapted strain of Amycolatopsis sp. ATCC 39116","authors":"Rasika V. Tupe, Nitesh K. Singh, Annamma A. Odaneth","doi":"10.1002/btpr.3417","DOIUrl":"10.1002/btpr.3417","url":null,"abstract":"Maize bran, an agro-processing waste residue, is a good source of ferulic acid that can be further valorized for vanillin production. However, extraction of ferulic acid from natural sources has been challenging due to low concentrations and intensive extraction procedures. In the present work, ferulic acid streams (purities ranging from 5% to 75%) extracted from maize bran using thermochemical methods were evaluated for biotransformation to vanillin, employing Amycolatopsis sp. as a whole-cell biocatalyst. Initial adaptation studies were critical in improving ferulic acid assimilation and its conversion to vanillin by 65% and 56%, respectively by the fourth adaptation cycle. The effect of cell's physiological states and vanillic acid supplementation on vanillin production was studied using standard ferulic acid as a substrate in an effort to achieve further improvement in vanillin yield. In the presence of vanillic acid, 18 h cultured cells using 2 g/L of standard and isolated ferulic acid produced vanillin concentrations of up to 0.71 and 0.48 g/L, respectively. Furthermore, intermediates involved in the ferulic acid catabolic pathway and their interrelations were studied using GC–MS analysis. Results indicated that two different routes were involved in the catabolism of standard ferulic acid, and similar metabolic routes were observed for an isolated ferulic acid stream. These findings effectively evaluated isolated ferulic acid for sustainable vanillin production while reducing agro-industrial waste pollution.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A deep-well plate enabled automated high-throughput cell line development platform 深孔板自动化高通量细胞系开发平台。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-20 DOI: 10.1002/btpr.3442

Xiaoyan Tang, Jorge Quiroz, Yixiao Zhang, Jessica Pan, Zhong Lai, Zhimei Du, Ren Liu

{"title":"A deep-well plate enabled automated high-throughput cell line development platform","authors":"Xiaoyan Tang, Jorge Quiroz, Yixiao Zhang, Jessica Pan, Zhong Lai, Zhimei Du, Ren Liu","doi":"10.1002/btpr.3442","DOIUrl":"10.1002/btpr.3442","url":null,"abstract":"Cell line development (CLD) plays a crucial role in the manufacturing process development of therapeutic biologics. Most biologics are produced in Chinese hamster ovary (CHO) cell. Because of the nature of random transgene integration in CHO genome and CHO's inherent plasticity, stable CHO transfectants usually have a vast diversity in productivity, growth, and product quality. Thus, we often must resort to screening a large number of cell pools and clones to increase the probability of identifying the ideal production cell line, which is a very laborious and resource-demanding process. Here we have developed a deep-well plate (DWP) enabled high throughput (DEHT) CLD platform using 24-well DWP (24DWP), liquid handler, and other automation components. This platform has capabilities covering the key steps of CLD including cell passaging, clone imaging and expansion, and fed-batch production. We are the first to demonstrate the suitability of 24DWP for CLD by confirming minimal well-to-well and plate-to-plate variability and the absence of well-to-well cross contamination. We also demonstrated that growth, production, and product quality of 24DWP cultures were comparable to those of conventional shake flask cultures. The DEHT platform enables scientists to screen five times more cultures than the conventional CLD platform, thus significantly decreases the resources needed to identify an ideal production cell line for biologics manufacturing.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139911925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of PDL1 positive cancer cell-specific binding activity of recombinant anti-PDL1 scFv 评估重组抗 PDL1 scFv 的 PDL1 阳性癌细胞特异性结合活性。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-20 DOI: 10.1002/btpr.3439

Sun-Hee Kim, Hae-Min Park, Hee-Jin Jeong

引用次数: 0

Leveraging machine learning to dissect role of combinations of amino acids in modulating the effect of zinc on mammalian cell growth 利用机器学习剖析氨基酸组合在调节锌对哺乳动物细胞生长的影响中的作用。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-15 DOI: 10.1002/btpr.3436

Ujjiti Pandey, Indrani Madhugiri, Chetan Gadgil, Mugdha Gadgil

{"title":"Leveraging machine learning to dissect role of combinations of amino acids in modulating the effect of zinc on mammalian cell growth","authors":"Ujjiti Pandey, Indrani Madhugiri, Chetan Gadgil, Mugdha Gadgil","doi":"10.1002/btpr.3436","DOIUrl":"10.1002/btpr.3436","url":null,"abstract":"Although the contributions of individual components of cell culture media are largely known, their combinatorial effects are far less understood. Experiments varying one component at a time cannot identify combinatorial effects, and analysis of the large number of experiments required to decipher such effects is challenging. Machine learning algorithms can help in the analysis of such datasets to identify multi-component interactions. Zinc toxicity in vitro is known to change depending on amino acid concentration in the extracellular medium. Multiple amino acids are known to be involved in this protection. Thirty-two amino acid compositions were formulated to evaluate their effect on the growth of CHO cells under high zinc conditions. A sequential machine learning analysis methodology was used, which led to the identification of a set of amino acids (threonine, proline, glutamate, aspartate, asparagine, and tryptophan) contributing to protection from zinc. Our results suggest that a decrease in availability of these set of amino acids due to consumption may affect cell growth in media formulated with high zinc concentrations, and in contrast, normal levels of these amino acids are associated with better tolerance to high zinc concentration. Our sequential analysis method may be similarly employed for high throughput medium design and optimization experiments to identify interactions among a large number of cell culture medium components.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of inner diameter, filter length, and pore size on hollow fiber filter fouling during perfusion cell culture 内径、过滤器长度和孔径对灌流细胞培养过程中中空纤维过滤器堵塞的影响。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-11 DOI: 10.1002/btpr.3440

Dominique WuDunn, Andrea Squeri, Jimmy Vu, Ashna Dhingra, Jon Coffman, Ken Lee

{"title":"Effect of inner diameter, filter length, and pore size on hollow fiber filter fouling during perfusion cell culture","authors":"Dominique WuDunn, Andrea Squeri, Jimmy Vu, Ashna Dhingra, Jon Coffman, Ken Lee","doi":"10.1002/btpr.3440","DOIUrl":"10.1002/btpr.3440","url":null,"abstract":"As the need for higher volumetric productivity in biomanufacturing grows, biopharmaceutical companies are increasingly investing in a perfusion cell culture process, most commonly one that uses a hollow fiber filter as the cell retention device. A current challenge with using hollow fiber filters is fouling of the membrane, which reduces product sieving and can increase transmembrane pressure (TMP) past process limitations. In this work, the impact of hollow fiber filter geometries on product sieving and hydraulic membrane resistance profiles is evaluated in a tangential flow filtration (TFF) perfusion system. The hollow fibers tested had lengths ranging from 19.8 to 41.5 cm, inner diameters (IDs) ranging from 1.0 to 2.6 mm, and pore sizes of 0.2 or 0.65 μm. The results showed that the shortest hollow fibers experienced higher product sieving while larger IDs contributed to both higher product sieving and lower hydraulic membrane resistances, illustrating the impact of filter geometry on process performance. The results also showed 0.2 μm pore size filters maintain higher product sieving, but also higher membrane resistances compared to 0.65 μm pore size filters. This study highlights the need for optimized hollow fiber filter geometries to maximize use of the membrane area, which in turn can reduce production costs and increase scalability of the perfusion process.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.3440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing multiproduct resin reuse for development and clinical manufacturing of an antibody-based therapeutic 推进多产品树脂再利用，用于抗体疗法的开发和临床生产。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-09 DOI: 10.1002/btpr.3434

Hong Li, Patricia Rose, Patricia Rowicki, Collette Cutler, Jeffrey T. McPhee, Claudia Frey, Linda Lemieux, Gerald Pelette, Joo Kok Ang, Ren Liu, Douglas D. Richardson

{"title":"Advancing multiproduct resin reuse for development and clinical manufacturing of an antibody-based therapeutic","authors":"Hong Li, Patricia Rose, Patricia Rowicki, Collette Cutler, Jeffrey T. McPhee, Claudia Frey, Linda Lemieux, Gerald Pelette, Joo Kok Ang, Ren Liu, Douglas D. Richardson","doi":"10.1002/btpr.3434","DOIUrl":"10.1002/btpr.3434","url":null,"abstract":"Chromatography resins used for purifying biopharmaceuticals are generally dedicated to a single product. For clinical manufacturing, this can result in resin being used only for a fraction of its potential lifetime. Extending the use of resins to multiple products can significantly reduce resin waste and cost. It can also improve manufacturing flexibility in case of raw material shortage during times such as the COVID-19 pandemic. The work presented herein describes an overarching multiproduct resin reuse (MRR) strategy, which includes a risk assessment, strategic planning, small-scale feasibility runs, and the successful execution of the MRR strategy to support Good manufacturing practice (GMP) clinical manufacturing of an antibody-based therapeutic. Specifically, an anion exchange (AEX) and cation exchange (CEX) MRR strategy is described. Clearance of carryover biological product is demonstrated by first cleaning the AEX and CEX manufacturing columns with sodium hydroxide to ensure inactivation and degradation of the carryover protein and followed by a blank buffer elution that is tested using various analytical methodologies to ensure reduction of the carryover protein to an acceptable level. To our knowledge, this is the first time an MRR approach has been successfully implemented and submitted to health authorities to support biologic GMP clinical manufacture.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.3434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implementation of mDoE-methods to a microcarrier-based expansion processes for mesenchymal stem cells 将 mDoE 方法应用于基于微载体的间充质干细胞扩增过程。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-09 DOI: 10.1002/btpr.3429

Kim B. Kuchemüller, Ralf Pörtner, Johannes Möller

{"title":"Implementation of mDoE-methods to a microcarrier-based expansion processes for mesenchymal stem cells","authors":"Kim B. Kuchemüller, Ralf Pörtner, Johannes Möller","doi":"10.1002/btpr.3429","DOIUrl":"10.1002/btpr.3429","url":null,"abstract":"The need for advanced therapy medicinal products (ATMPs) has gained increased attention in recent years. In this respect, a well-designed cell expansion process is needed to efficiently manufacture the required number of cells with the desired product quality. This step is challenging due to the biological complexity of the respective primary cell (e.g., mesenchymal stem cells (MSC)) and the usage of microcarrier-based expansion systems. One accelerating approach for process design is model-assisted Design of Experiments (mDoE) combining mathematical process models and statistical tools. In this study, the mDoE workflow was used for the development of an expansion processes with human immortalized mesenchymal stem cells (hMSC-TERT) and the aim of maximizing cell yield assuming only a limited amount of prior knowledge at a very early stage of development. First, suitable microcarriers for expansion in shake flasks were screened and the differentiation of the cells was proven. Second, initial experiments were performed to generate prior knowledge, which was then used to set up the mathematical model and to estimate the model parameters. Finally, the mDoE was used to determine and evaluate the design space to be performed experimentally. Overall, a cell expansion process using microcarriers in a shake flask culture was successfully implemented and a significant increase in cell yield (up to 6,2-fold) was achieved compared to literature.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.3429","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of flux and shear rate on E. coli recovery in tangential flow filtration through a single hollow fiber 流量和剪切率对单根中空纤维切向流过滤中大肠杆菌回收率的影响。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2024-02-08 DOI: 10.1002/btpr.3432

Jessica Zuponcic, Fernanda Cunha, Grant Springer, Eduardo Ximenes, Michael R. Ladisch

{"title":"Effect of flux and shear rate on E. coli recovery in tangential flow filtration through a single hollow fiber","authors":"Jessica Zuponcic, Fernanda Cunha, Grant Springer, Eduardo Ximenes, Michael R. Ladisch","doi":"10.1002/btpr.3432","DOIUrl":"10.1002/btpr.3432","url":null,"abstract":"Pathogenic bacteria which enter a viable but non-culturable (VBNC) state impede efforts to reach detectable concentrations required for PCR methods. This motivated a strategy for tangential flow filtration to concentrate bacteria in aqueous samples while maintaining the bacteria in a viable state, maximizing their recovery and achieving high fluxes through a single hollow fiber membrane. Filtrations were carried out for green fluorescent protein (GFP) E. coli at high shear rates (up to 27,000 sec−1) through 0.2 μm cut-off polyethersulfone (PES) microfilter membranes or 50 kDa polysulfone (PS) ultrafilter membranes. High shear minimized bacterial attachment on membrane surfaces, which would otherwise occur due to forced convection of the particles to the membrane surface at high flux conditions. Single fiber filter modules were constructed to facilitate concentration of Escherichia coli at fluxes ranging from 55 to 4500 L m−2 h−1. The effect of high shear rates on bacterial viability was found to be minimal with bacterial losses during filtration caused principally by their accumulation on the membrane surface. Recoveries of 90% were achievable at high shear rates when the average flux was ≤300 L m−2 h−1. This corresponded to a 3-h filtration time for a 225 mL sample through a single hollow fiber. Detectable bacteria concentrations of 1800 colony-forming unit (CFU)/mL were achieved for starting concentrations of 140 CFU/mL.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.3432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0