Biochemical Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
Biochemical Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
Int J Biol Macromol. 2024 May;266(Pt 2):131379. doi: 10.1016/j.ijbiomac.2024.131379. Epub 2024 Apr 3.
Monoclonal antibodies (mAbs) are laboratory-based engineered protein molecules with a monovalent affinity or multivalent avidity towards a specific target or antigen, which can mimic natural antibodies that are produced in the human immune systems to fight against detrimental pathogens. The recombinant mAb is one of the most effective classes of biopharmaceuticals produced in vitro by cloning and expressing synthetic antibody genes in a suitable host. Yeast is one of the potential hosts among others for the successful production of recombinant mAbs. However, there are very few yeast-derived mAbs that got the approval of the regulatory agencies for direct use for treatment purposes. Certain challenges encountered by yeasts for recombinant antibody productions need to be overcome and a few considerations related to antibody structure, host engineering, and culturing strategies should be followed for the improved production of mAbs in yeasts. In this review, the drawbacks related to the metabolic burden of the host, culturing conditions including induction mechanism and secretion efficiency, solubility and stability, downstream processing, and the pharmacokinetic behavior of the antibody are discussed, which will help in developing the yeast hosts for the efficient production of recombinant mAbs.
单克隆抗体(mAbs)是实验室中基于工程设计的蛋白质分子,对特定的靶标或抗原具有单价亲和力或多价亲合力,可模拟人体免疫系统产生的天然抗体,以抵御有害病原体。重组 mAb 是通过在合适的宿主中克隆和表达合成抗体基因在体外产生的最有效的生物制药之一。酵母是其他潜在宿主之一,可成功生产重组 mAb。然而,仅有极少数的酵母来源 mAb 获得监管机构的批准,可直接用于治疗目的。需要克服酵母在重组抗体生产方面遇到的某些挑战,并且应遵循与抗体结构、宿主工程和培养策略相关的一些考虑因素,以提高酵母中 mAb 的产量。在本文综述中,讨论了与宿主的代谢负担、培养条件(包括诱导机制和分泌效率)、溶解度和稳定性、下游处理以及抗体的药代动力学行为相关的缺点,这将有助于开发用于高效生产重组 mAb 的酵母宿主。