基于人单克隆抗体寡克隆混合物的实验性重组蛇咬伤抗蛇毒血清的单批次表达。
Single-Batch Expression of an Experimental Recombinant Snakebite Antivenom Based on an Oligoclonal Mixture of Human Monoclonal Antibodies.
发表日期:2024 Oct
作者:
Anna C Adams, Lise M Grav, Shirin Ahmadi, Camilla Holst Dahl, Anne Ljungars, Andreas H Laustsen, Lars K Nielsen
来源:
Biotechnology Journal
摘要:
寡克隆抗体是经过精心定义的单克隆抗体混合物,对于治疗感染和癌症等复杂疾病很有价值。除了这些医学领域之外,它们还可以用于治疗蛇咬伤,重组产生的单克隆人类抗体可以克服传统抗蛇毒血清的许多缺点。然而,在工业环境中生产多个单独批次的单克隆抗体需要高昂的成本。因此,通过在单个批次中混合多个抗体产生细胞系以仅具有一个上游和下游过程来生产寡克隆抗体是有吸引力的。在这项研究中,我们选择了四种针对不同蛇类(如曼巴蛇和眼镜蛇)毒液中发现的不同毒素的抗体,并生成了稳定的抗体产生细胞系。共培养后,我们发现细胞系比率在 7 天内保持稳定。纯化的寡克隆抗体混合物含有预期的抗体浓度,并按预期与目标毒素结合。因此,这些结果为在单批次中混合多个细胞系以重组生产定制抗蛇毒血清的策略提供了概念证明,该策略可用于治疗蛇咬伤中毒以及寡克隆抗体混合物可以发挥作用的其他领域。© 2024作者。生物技术杂志由 Wiley‐VCH GmbH 出版。
Oligoclonal antibodies, which are carefully defined mixtures of monoclonal antibodies, are valuable for the treatment of complex diseases, such as infectionss and cancer. In addition to these areas of medicine, they could be utilized for the treatment of snakebite envenoming, where recombinantly produced monoclonal human antibodies could overcome many of the drawbacks accompanying traditional antivenoms. However, producing multiple individual batches of monoclonal antibodies in an industrial setting is associated with significant costs. Therefore, it is attractive to produce oligoclonal antibodies by mixing multiple antibody-producing cell lines in a single batch to have only one upstream and downstream process. In this study, we selected four antibodies that target different toxins found in the venoms of various elapid snake species, such as mambas and cobras, and generated stable antibody-producing cell lines. Upon co-cultivation, we found the cell line ratios to be stable over 7 days. The purified oligoclonal antibody cocktail contained the anticipated antibody concentrations and bound to the target toxins as expected. These results thus provide a proof of concept for the strategy of mixing multiple cell lines in a single batch to manufacture tailored antivenoms recombinantly, which could be utilized for the treatment of snakebite envenoming and in other fields where oligoclonal antibody mixtures could find utility.© 2024 The Author(s). Biotechnology Journal published by Wiley‐VCH GmbH.