IBB - Institute for Biotechnology and Bioengineering, University of Minho, Braga, Portugal.
Eur J Pharm Biopharm. 2010 Feb;74(2):127-38. doi: 10.1016/j.ejpb.2009.10.002. Epub 2009 Oct 22.
Monoclonal antibodies (mAbs) are currently used for many diagnostic and therapeutic applications. The high demand for these biopharmaceuticals has led to the development of large-scale manufacturing processes, with productivity improvements being mainly achieved by optimization of bioreactor systems. However, more recently, the early steps of production, previous to bioreactor culture, have been presented as alternative areas where productivity enhancements can be achieved. Thus, this review describes the progress made for the improvement of productivity in mammalian expression systems for the high production of mAbs. Advances in the development of mAb-producing cell lines are being made, particularly regarding expression vector design and methods used for transfection, with the intent to create a reproducible methodology. Selection of the most suitable clones is also a critical step that can be improved, by including variables other than the expression level, which is still the common practice. Furthermore, strategies of cell engineering, although still mostly based on trial-and-error experimentation and not in standard protocols, hold great interest to improve cell growth and productivity, as well as product quality in the future. Improvements of the initial steps of the production process would not only result in cells with higher expression ability, but would also speed-up the process development.
单克隆抗体 (mAbs) 目前被广泛应用于诊断和治疗领域。这些生物制药的高需求促使大规模生产工艺得以发展，生物反应器系统的优化主要提高了生产效率。然而，最近，生物反应器培养之前的生产早期步骤已被视为提高生产效率的另一个可行方向。因此，本文综述了提高哺乳动物表达系统生产 mAb 生产效率的进展。在提高 mAb 生产细胞系的生产效率方面取得了进展，特别是在表达载体设计和转染方法方面，旨在建立可重复的方法。选择最合适的克隆也是一个关键步骤，可以通过包括除表达水平以外的其他变量来改进，这仍然是常见的做法。此外，细胞工程策略虽然仍然主要基于反复试验的实验，而不是标准协议，但对于提高细胞生长和生产效率以及未来产品质量具有重要意义。改进生产过程的初始步骤不仅可以使细胞具有更高的表达能力，还可以加快工艺开发。
