Zhang Jun-He, Shan Lin-Lin, Liang Fan, Du Chen-Yang, Li Jing-Jing
Institutes of Health Central Plains, Xinxiang Medical University, Xinxiang, China.
Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, China.
Front Bioeng Biotechnol. 2022 Mar 4;10:856049. doi: 10.3389/fbioe.2022.856049. eCollection 2022.
Recombinant antibodies are rapidly developing therapeutic agents; approximately 40 novel antibody molecules enter clinical trials each year, most of which are produced from Chinese hamster ovary (CHO) cells. However, one of the major bottlenecks restricting the development of antibody drugs is how to perform high-level expression and production of recombinant antibodies. The high-efficiency expression and quality of recombinant antibodies in CHO cells is determined by multiple factors. This review provides a comprehensive overview of several state-of-the-art approaches, such as optimization of gene sequence of antibody, construction and optimization of high-efficiency expression vector, using antibody expression system, transformation of host cell lines, and glycosylation modification. Finally, the authors discuss the potential of large-scale production of recombinant antibodies and development of culture processes for biopharmaceutical manufacturing in the future.
重组抗体是快速发展的治疗药物；每年约有40种新型抗体分子进入临床试验，其中大部分是由中国仓鼠卵巢（CHO）细胞生产的。然而，限制抗体药物发展的主要瓶颈之一是如何进行重组抗体的高水平表达和生产。CHO细胞中重组抗体的高效表达和质量由多种因素决定。本文综述了几种先进的方法，如抗体基因序列优化、高效表达载体的构建与优化、抗体表达系统的使用、宿主细胞系的改造以及糖基化修饰。最后，作者讨论了重组抗体大规模生产的潜力以及未来生物制药生产培养工艺的发展。
