Strategies for High-Titer and High-Quality Monoclonal Antibody Production: Cell Line Construction, Culture Medium Development, and Process Regulation in Bioreactors

Abstract

With the widespread application of monoclonal antibodies (mAbs) and their derivatives in biopharmaceuticals, upstream production processes face the dual challenge of increasing yield while ensuring product consistency. This review systematically summarizes the full technological chain for efficient and high-quality mAb production, focusing on three levels: cell line construction, culture medium development, and process regulation in bioreactors, and highlights their key strategies, mechanisms, and synergistic relationships. The cutting-edge strategies for cell line construction aim to improve host cell performance by optimizing carbon flux distribution, protein folding and secretion, and cell survival. In culture medium development, approaches including carbon source substitution, precise amino acid feeding, autophagy modulation, metal ion supplementation, and oxidative stress control can enhance nutrient supply, reduce accumulation of metabolic byproducts, and regulate key quality attributes. As for process regulation in bioreactors, parameters such as pH, temperature, agitation rate, aeration strategy, and perfusion rate jointly influence mass transfer efficiency, metabolic homeostasis, cell viability, and product quality under high-density culture. Furthermore, process development for mAb production has shifted from empirical optimization of individual modules to a systems-level integration of intrinsic cellular performance, culture environment, and process regulation. Looking forward, artificial intelligence is expected to drive antibody manufacturing toward predictive design, dynamic feedback control, and intelligent scale-up. This review provides theoretical guidance and technical strategies for constructing high-yield, robust, and scalable industrial antibody production platforms.