Department of Physiology, Center of Physiology and Pharmacology and Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria.
Department of Physiology, Center of Physiology and Pharmacology and Comprehensive Cancer Center (CCC), Medical University of Vienna, 1090 Vienna, Austria.
J Biotechnol. 2021 Apr 10;331:1-13. doi: 10.1016/j.jbiotec.2021.02.013. Epub 2021 Mar 6.
Despite the essential role secretory IgAs play in the defense against pathogenic invasion and the proposed value of recombinant secretory IgAs as novel therapeutics, currently there are no IgA-based therapies in clinics. Secretory IgAs are complex molecules and the major bottleneck limiting their therapeutic potential is a reliable recombinant production system. In this report, we addressed this issue and established a fast and robust production method for secretory IgAs in CHO-K1 cells using BAC-based expression vectors. As a proof of principle, we produced IgAs against Clostridium difficile toxins TcdA and TcdB. Recombinant secretory IgAs produced using our expression system showed comparable titers to IgGs, widely used as therapeutic biologicals. Importantly, secretory IgAs produced using our method were functional and could efficiently neutralize Clostridium difficile toxins TcdA and TcdB. These results show that recombinant secretory IgAs can be efficiently produced, thus opening the possibility to use them as therapeutic agents in clinics.
尽管分泌型 IgA 在抵御病原入侵方面发挥着重要作用，并且重组分泌型 IgA 被提议作为新型治疗药物具有潜在价值，但目前临床上尚无基于 IgA 的治疗方法。分泌型 IgA 是复杂的分子，限制其治疗潜力的主要瓶颈是可靠的重组生产系统。在本报告中，我们解决了这个问题，并使用基于 BAC 的表达载体在 CHO-K1 细胞中建立了分泌型 IgA 的快速、稳健的生产方法。作为原理验证，我们生产了针对艰难梭菌毒素 TcdA 和 TcdB 的 IgA。使用我们的表达系统生产的重组分泌型 IgA 的效价与 IgG 相当，IgG 广泛用作治疗性生物制剂。重要的是，使用我们的方法生产的分泌型 IgA 具有功能，可以有效中和艰难梭菌毒素 TcdA 和 TcdB。这些结果表明可以有效地生产重组分泌型 IgA，从而为将其用作临床治疗药物开辟了可能性。
