Fixing the Fc of plantibodies

Abstract

Plant Science Plants offer a cost-effective means to produce therapeutically useful monoclonal antibodies. However, antibodies produced in plants differ from those produced in mammalian cells. Notably, the glycan composition of plant antibodies can affect their binding activity. Stelter et al. generated variants of a broadly neutralizing HIV monoclonal antibody in the plant Nicotiana benthamiana that differed by glycosylation. Plant-generated antibodies with typical plant glycosylation patterns were less able to engage with the cell-surface receptors required for immune activation. However, cell-binding affinity was successfully improved by targeted glycoengineering. The plant-produced antibodies were also more susceptible to oxidation of methionine residues in the Fc region. Oxidation reduced the affinity of the antibodies for the protective neonatal Fc receptor, which in turn reduced their half-life and therapeutic window. This phenomenon requires a solution before plant-produced antibodies can fulfill their therapeutic promise. Plant Biotechnol. J. 18 , 402 (2020).