Honda Shinya, Sasaki Akira, Senga Yukako, Ooishi Ayako
Molecular Biosystems Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Anal Chem. 2025 Jun 10;97(22):11526-11535. doi: 10.1021/acs.analchem.5c00396. Epub 2025 May 23.
Antibody aggregation is a significant challenge in biopharmaceutical development, affecting drug efficacy and safety. This study applies fluorescence cross-correlation spectroscopy (FCCS) to analyze antibody aggregation, offering a novel approach to understanding this critical process. Our results demonstrated that aggregation can occur without species barriers, as evidenced by the correlated diffusion of different types of stressed antibodies. The absence of a species barrier is significant in elucidating aggregation mechanisms and ensuring the quality of therapeutic antibodies, particularly in oligoclonal formulations. Furthermore, we observed that the aggregation propensity of the antibody fragments (Fab and Fc) differed from that of full-length antibodies, emphasizing the need for a comprehensive analysis of both full-length antibodies and their fragments. Additionally, the self-aggregation propensity of fragments does not always align with their heteroaggregation propensity with preformed antibody aggregates. These findings emphasize the importance of advanced analytical methods to track heterogeneous aggregates accurately and provide insights into the aggregation dynamics of therapeutic antibodies under various conditions.
抗体聚集是生物制药研发中的一项重大挑战，会影响药物疗效和安全性。本研究应用荧光互相关光谱法（FCCS）分析抗体聚集，为理解这一关键过程提供了一种新方法。我们的结果表明，聚集可跨越物种屏障发生，不同类型应激抗体的相关扩散证明了这一点。物种屏障的不存在对于阐明聚集机制和确保治疗性抗体的质量具有重要意义，特别是在寡克隆制剂中。此外，我们观察到抗体片段（Fab和Fc）的聚集倾向与全长抗体不同，这强调了对全长抗体及其片段进行全面分析的必要性。此外，片段的自聚集倾向并不总是与其与预先形成的抗体聚集体的异源聚集倾向一致。这些发现强调了先进分析方法对于准确追踪异质聚集体以及深入了解各种条件下治疗性抗体聚集动力学的重要性。
