Trastuzumab and Pertuzumab Plant Biosimilars: Modification of Asn297-linked Glycan of the mAbs Produced in a Plant with Fucosyltransferase and Xylosyltransferase Gene Knockoutsстатья
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Аннотация:Plant biosimilars of anticancer therapeutic antibodies are of interest not only because of the prospects of their
practical use, but also as an instrument and object for study of plant protein glycosylation. In this work, we first designed a
pertuzumab plant biosimilar (PPB) and investigated the composition of its Asn297linked glycan in comparison with
trastuzumab plant biosimilar (TPB). Both biosimilars were produced in wildtype (WT) Nicotiana benthamiana plant (PPB
WT and TPBWT) and transgenic ΔXTFT N. benthamiana plant with XT and FT genes knockout (PPBΔXTFT and TPB
ΔXTFT). Western blot analysis with antiα1,3fucose and antixylose antibodies, as well as a test with peptideNglycosi
dase F, confirmed the absence of α1,3fucose and xylose in the Asn297linked glycan of PPBΔXTFT and TPBΔXTFT.
Peptide analysis followed by the identification of glycomodified peptides using MALDITOF/TOF showed that PPBWT
and TPBWT Asn297linked glycans are mainly of complex type GnGnXF. The core of PPBWT and TPBWT Asn297
linked GnGntype glycan contains α1,3fucose and β1,2xylose, which, along with the absence of terminal galactose and
sialic acid, distinguishes these plant biosimilars from human IgG. Analysis of TPBΔXTFT total carbohydrate content indi
cates the possibility of changing the composition of the carbohydrate profile not only of the Fc, but also of the Fab portion
of an antibody produced in transgenic ΔXTFT N. benthamiana plants. Nevertheless, study of the antigenbinding capacity
of the biosimilars showed that absence of xylose and fucose residues in the Asn297linked glycans does not affect the abili
ty of the glycomodified antibodies to interact with HER2/neu positive cancer cells.