{"title":"使用 CHO-MK 细胞和特定培养基在常规喂养批次培养中提高单克隆抗体的生产效率。","authors":"Hisashi Saeki, Kaori Fueki, Naoki Maeda","doi":"10.1007/s10616-024-00669-4","DOIUrl":null,"url":null,"abstract":"<p><p>Chinese hamster ovary (CHO) cell lines, derived as subclones from the original CHO cell line, are widely used hosts for current biopharmaceutical productions. Recently, a highly proliferative host cell line, CHO-MK, was established from the Chinese hamster ovary tissue. In this study, we assessed the fundamental culture characteristics and capabilities of CHO-MK cells for monoclonal antibody (mAb) production using specified chemically defined media. To achieve this, we established fed-batch cultures of model CHO-MK cells in shake flasks and ambr15 and 2 L bioreactors under various conditions. The mAb-producing CHO-MK cell line A produced 12.6 g/L of antibody within 7 days in the fed-batch culture using a 2 L bioreactor, with a seeding density of 1 × 10<sup>6</sup> cells/mL. This performance corresponded to a space-time yield of 1.80 g/L/day, representing a productivity level that could be challengingly attained in fed-batch cultures using conventional CHO cells. In addition, when we subjected six different mAb-producing CHO-MK cell lines to fed-batch culture in the ambr15 bioreactor for 7 days, the antibody production ranged between 5.1 and 10.8 g/L, confirming that combining CHO-MK cells and specified media leads to enhanced versatility. These discoveries underscore that CHO-MK cells combined with specified media might represent a next-generation production platform, which could potentially respond to an increasing demand for antibody drugs, reducing production costs, and shortening antibody drug development times. This study is expected to serve as a benchmark for future production process development using CHO-MK cells.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"1"},"PeriodicalIF":2.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573942/pdf/","citationCount":"0","resultStr":"{\"title\":\"Enhancing monoclonal antibody production efficiency using CHO-MK cells and specific media in a conventional fed-batch culture.\",\"authors\":\"Hisashi Saeki, Kaori Fueki, Naoki Maeda\",\"doi\":\"10.1007/s10616-024-00669-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chinese hamster ovary (CHO) cell lines, derived as subclones from the original CHO cell line, are widely used hosts for current biopharmaceutical productions. Recently, a highly proliferative host cell line, CHO-MK, was established from the Chinese hamster ovary tissue. In this study, we assessed the fundamental culture characteristics and capabilities of CHO-MK cells for monoclonal antibody (mAb) production using specified chemically defined media. To achieve this, we established fed-batch cultures of model CHO-MK cells in shake flasks and ambr15 and 2 L bioreactors under various conditions. The mAb-producing CHO-MK cell line A produced 12.6 g/L of antibody within 7 days in the fed-batch culture using a 2 L bioreactor, with a seeding density of 1 × 10<sup>6</sup> cells/mL. This performance corresponded to a space-time yield of 1.80 g/L/day, representing a productivity level that could be challengingly attained in fed-batch cultures using conventional CHO cells. In addition, when we subjected six different mAb-producing CHO-MK cell lines to fed-batch culture in the ambr15 bioreactor for 7 days, the antibody production ranged between 5.1 and 10.8 g/L, confirming that combining CHO-MK cells and specified media leads to enhanced versatility. These discoveries underscore that CHO-MK cells combined with specified media might represent a next-generation production platform, which could potentially respond to an increasing demand for antibody drugs, reducing production costs, and shortening antibody drug development times. 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引用次数: 0
摘要
中国仓鼠卵巢(CHO)细胞系是从原始 CHO 细胞系中衍生出来的亚克隆,是目前生物制药生产中广泛使用的宿主细胞系。最近,从中国仓鼠卵巢组织中建立了一种高增殖宿主细胞系 CHO-MK。在本研究中,我们评估了 CHO-MK 细胞的基本培养特性和使用特定化学定义培养基生产单克隆抗体(mAb)的能力。为此,我们在摇瓶、ambr15 和 2 L 生物反应器中建立了各种条件下的模型 CHO-MK 细胞批量喂养培养。在使用 2 L 生物反应器进行的喂养批量培养中,产生 mAb 的 CHO-MK 细胞系 A 在 7 天内产生了 12.6 g/L 的抗体,细胞播种密度为 1 × 106 cells/mL。这一表现相当于 1.80 克/升/天的时空产量,代表了使用传统 CHO 细胞进行喂养式批次培养时难以达到的生产率水平。此外,当我们在 ambr15 生物反应器中对六种不同的生产 mAb 的 CHO-MK 细胞系进行为期 7 天的喂养批量培养时,抗体产量介于 5.1 克/升和 10.8 克/升之间,这证实了将 CHO-MK 细胞与特定培养基结合可提高多功能性。这些发现突出表明,CHO-MK 细胞与特定培养基的结合可能代表着新一代的生产平台,有可能满足日益增长的抗体药物需求,降低生产成本,缩短抗体药物开发时间。这项研究有望成为未来使用 CHO-MK 细胞开发生产工艺的基准。
Enhancing monoclonal antibody production efficiency using CHO-MK cells and specific media in a conventional fed-batch culture.
Chinese hamster ovary (CHO) cell lines, derived as subclones from the original CHO cell line, are widely used hosts for current biopharmaceutical productions. Recently, a highly proliferative host cell line, CHO-MK, was established from the Chinese hamster ovary tissue. In this study, we assessed the fundamental culture characteristics and capabilities of CHO-MK cells for monoclonal antibody (mAb) production using specified chemically defined media. To achieve this, we established fed-batch cultures of model CHO-MK cells in shake flasks and ambr15 and 2 L bioreactors under various conditions. The mAb-producing CHO-MK cell line A produced 12.6 g/L of antibody within 7 days in the fed-batch culture using a 2 L bioreactor, with a seeding density of 1 × 106 cells/mL. This performance corresponded to a space-time yield of 1.80 g/L/day, representing a productivity level that could be challengingly attained in fed-batch cultures using conventional CHO cells. In addition, when we subjected six different mAb-producing CHO-MK cell lines to fed-batch culture in the ambr15 bioreactor for 7 days, the antibody production ranged between 5.1 and 10.8 g/L, confirming that combining CHO-MK cells and specified media leads to enhanced versatility. These discoveries underscore that CHO-MK cells combined with specified media might represent a next-generation production platform, which could potentially respond to an increasing demand for antibody drugs, reducing production costs, and shortening antibody drug development times. This study is expected to serve as a benchmark for future production process development using CHO-MK cells.
期刊介绍:
The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.