Glycoengineering of plant-produced Pembrolizumab enhances FcRn binding and extends serum half-life in mice.

ABSTRACT: Plant systems offer scalable and cost-effective platforms for antibody production, but plant-specific glycans may affect pharmacokinetics and immunogenicity. To evaluate the impact of Fc glycosylation, four Pembrolizumab glycovariants were generated in Nicotiana benthamiana: wild-type glycosylation (Pembro-WT), high-mannose with SEKDEL (Pembro-KD), aglycosylated N297A mutant (Pembro-NG), and a core fucose/xylose-deficient variant (Pembro-XF). Glycoproteins were transiently expressed either in wild-type or ΔXF plants, purified, and characterized for glycan composition, in vitro binding, and in vivo pharmacokinetics. LC-MS confirmed distinct glycoform patterns, while PD-1 binding was retained across all variants. Pembro-XF showed the highest FcRn binding affinity and longest serum hal

SUBMITTER: Bulaon CJI 

PROVIDER: S-EPMC12523803 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature