Plant-derived Monoclonal Antibody Production: Historical Developments, Technological Advancements and Future Prospects

Plant-based platforms have emerged as a promising alternative technology for producing therapeutic monoclonal antibodies.They offer unique benefits compared to conventional mammalian cell culture systems with regard to their cost, production scale, and biological safety.Since antibody expression was reported for the first time in Nicotiana tabacum in the late 1980s, advancements in plant molecular farming techniques have facilitated the production of biofunctional antibodies with diverse structures, from immunoglobulin (Ig)G to secretory IgA.Specifically, Nicotiana benthamiana is a high-throughput, mass-production platform that reliably achieves high yields at the g/kg level within weeks through transient expression systems.Improvements in host optimization, good manufacturing practice-level production processes, and human N-glycan engineering have enhanced the functionality and consistency of antibodies.In general, ZMapp, a plant-derived Ebola virus antibody cocktail, and anti-CTLA-4 mAbs exhibited efficacy similar to that of mammalian cellderived antibodies.Additionally, next-generation antibodies, including PD-L1/CTLA-4 bispecific antibodies and SARS-CoV-2 antibodies, demonstrated clinical potential.However, standardization of the entire process, economical upstream biomass production, and downstream purification processes remain a significant challenge.The convergence of glycoengineering, advanced synthetic biology tools, and AI-driven culture control technologies holds promise for transforming plants into self-optimizing molecular farming platforms.Plant-based antibody systems are no longer just low-cost alternatives.They are being transformed into scalable and sustainable platforms for nextgeneration biomanufacturing.