Understanding and controlling the molecular mechanisms of protein aggregation in mAb therapeutics
Kuin Tian Pang, Yuansheng Yang, Wei Zhang, Ying Swan Ho, Pietro Sormanni, Thomas C. T. Michaels, Ian Walsh, Sean Chia
Abstract
In antibody development and manufacturing, protein aggregation is a common challenge that can lead to serious efficacy and safety issues. To mitigate this problem, it is important to investigate its molecular origins. This review discusses (1) our current molecular understanding and theoretical models of antibody aggregation, (2) how various stress conditions related to antibody upstream and downstream bioprocesses can trigger aggregation, and (3) current mitigation strategies employed towards inhibiting aggregation. We discuss the relevance of the aggregation phenomenon in the context of novel antibody modalities and highlight how in silico approaches can be exploited to mitigate it.