基于人单克隆抗体的寡克隆混合物的实验重组蛇咬抗蛇毒素的单批面表达
Single-Batch Expression of an Experimental Recombinant Snakebite Antivenom Based on an Oligoclonal Mixture of Human Monoclonal Antibodies
影响因子:3.10000
分区:生物学3区 / 生化研究方法3区 生物工程与应用微生物3区
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
摘要
少量克隆抗体是仔细定义的单克隆抗体混合物，对于治疗复杂疾病（例如感染和癌症）很有价值。除了这些医学领域，它们还可以用于治疗蛇咬蛋白，在该治疗中，重组产生的单克隆人类抗体可以克服伴随传统抗蛇毒的许多缺点。但是，在工业环境中生产多个单独的单克隆抗体与巨大的成本有关。因此，通过将多种抗体产生的细胞系混合到单批中，仅具有一个上游和下游过程来产生寡克隆抗体。在这项研究中，我们选择了四种靶向在各种雌性蛇种的毒液中发现不同毒素的抗体，例如mambas和cobras，并产生了稳定的产生抗体产生的细胞系。共培养后，我们发现细胞系比在7天内稳定。纯化的寡克隆抗体鸡尾酒含有预期的抗体浓度，并按预期与靶毒素结合。因此，这些结果为在单批次中混合多个细胞系以重组制造多个细胞系的策略提供了概念证明，可以将其用于治疗蛇咬蛋白含量的治疗以及其他寡聚抗体混合物可以找到实用性的领域。
Abstract
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.