Pan Jessica, McPhee Jeffrey, Dow Alex, Burke Daniel, Gupta Balrina, Rose Patricia, Wang Xiaowen, Pinto Nuno, Letarte Simon, Huang Ying, Li Guanghua Benson, Agarwal Kitty, Smith Katelyn, Liu Ren
Bioprocess R&D, Merck & Co., Inc, Rahway, NJ, USA.
Analytical R&D, Merck & Co., Inc, Rahway, NJ, USA.
BMC Biotechnol. 2025 May 7;25(1):33. doi: 10.1186/s12896-025-00968-4.
The use of non-clonal CHO cell derived materials for preclinical studies has been found to be a valuable approach to accelerate the development of monoclonal antibodies (mAbs) for first-in-human (FIH) studies. In a comprehensive study, we assessed the culture performance, productivity, and product quality of non-clonal cell lines compared with clonal cell lines expressing various biologic modalities to determine if this approach can be applied to complex molecules.
We evaluated a multi-specific antibody, a cytokine-Fc fusion protein, and a mAb produced using the stable pool, the pool of top clones, and the lead clone utilizing transposase-mediated integration. The results indicated that the attributes were comparable regardless of the source of cells. Building upon these findings, the study progressed to the preclinical manufacturing of two multi-specific antibodies using both the pool of top clones and the lead clone. Subsequently, clinical manufacturing of these multi-specific antibodies was performed using the lead clone. The batches produced with the pool of clones and the lead clone demonstrated a high level of comparability in culture performance, productivity, and product quality.
In conclusion, non-clonal CHO cell derived materials can be effectively utilized for preclinical studies of complex molecules without compromising their quality, allowing for accelerated development for FIH studies.
已发现使用非克隆CHO细胞衍生材料进行临床前研究是加速用于首次人体（FIH）研究的单克隆抗体（mAb）开发的一种有价值的方法。在一项全面研究中，我们评估了非克隆细胞系与表达各种生物学形式的克隆细胞系相比的培养性能、生产力和产品质量，以确定这种方法是否可应用于复杂分子。
我们评估了一种多特异性抗体、一种细胞因子-Fc融合蛋白以及使用稳定细胞池、顶级克隆池和利用转座酶介导整合的领先克隆生产的一种单克隆抗体。结果表明，无论细胞来源如何，这些属性都是可比的。基于这些发现，该研究进展到使用顶级克隆池和领先克隆对两种多特异性抗体进行临床前生产。随后，使用领先克隆对这些多特异性抗体进行临床生产。用克隆池和领先克隆生产的批次在培养性能、生产力和产品质量方面表现出高度的可比性。
总之，非克隆CHO细胞衍生材料可有效地用于复杂分子的临床前研究，而不会影响其质量，从而可加速FIH研究的开发。
