Differential N-glycosylation of a monoclonal antibody expressed in tobacco leaves with and without endoplasmic reticulum retention signal apparently induces similar in vivo stability in mice

Autor:	Ada, Triguero, Gleysin, Cabrera, Meilyn, Rodríguez, Jeny, Soto, Yasser, Zamora, Marlene, Pérez, Mark R, Wormald, José A, Cremata
Rok vydání:	2011
Předmět:	Models Molecular Hepatitis B virus Mice Inbred BALB C Glycosylation Protein Stability Antibodies Monoclonal Protein Sorting Signals Endoplasmic Reticulum Plants Genetically Modified Plantibodies Hepatitis B Antigens Plant Leaves Epitopes Mice Agrobacterium tumefaciens Gene Expression Regulation Plant Polysaccharides Tobacco Animals Female Rabbits Cloning Molecular Hepatitis B Antibodies
Zdroj:	Plant biotechnology journal. 9(9)
ISSN:	1467-7652
Popis:	Plant cells are able to perform most of the post-translational modifications that are required by recombinant proteins to achieve adequate bioactivity and pharmacokinetics. However, regarding N-glycosylation the processing of plant N-glycans in the Golgi apparatus displays major differences when compared with that of mammalian cells. These differences in N-glycosylation are expected to influence serum clearance rate of plant-derived monoclonal antibodies. The monoclonal antibody against the hepatitis B virus surface antigen expressed in Nicotiana tabacum leaves without KDEL endoplasmic reticulum (ER) retention signal (CB.Hep1(-)KDEL) and with a KDEL (Lys-Asp-Glu-Leu) fused to both IgG light and heavy chains (CB.Hep1(+)KDEL) were tested for in vivo stability in mice. Full characterization of N-glycosylation and aggregate formation in each monoclonal antibody batch was determined. The mouse counterpart (CB.Hep1) was used as control. Both (CB.Hep1(-)KDEL) and (CB.Hep1(+)KDEL) showed a faster initial clearance rate (first 24 h) compared with the analogous murine antibody while the terminal phase was similar in the three antibodies. Despite the differences between CB.Hep1(+)KDEL and CB.Hep1(-)KDEL N-glycans, the in vivo elimination in mice was indistinguishable from each other and higher than the murine monoclonal antibody. Molecular modelling confirmed that N-glycans linked to plantibodies were oriented away from the interdomain region, increasing the accessibility of the potential glycan epitopes by glycoprotein receptors that might be responsible for the difference in stability of these molecules.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::453c8c92d7db526009a037d1f28fb28d https://pubmed.ncbi.nlm.nih.gov/21819534 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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