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Trastuzumab and Pertuzumab Plant Biosimilars: Modification of Asn297-linked Glycan of the mAbs Produced in a Plant with Fucosyltransferase and Xylosyltransferase Gene Knockoutsстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 5 июня 2017 г.
- Авторы: Komarova T.V., Sheshukova E.V., Kosobokova E.N., Serebryakova M.V., Kosorukov V.S., Tashlitsky V.N., Dorokhov Y.L.
- Журнал: Biochemistry (Moscow)
- Том: 82
- Номер: 4
- Год издания: 2017
- Издательство: Pleiades Publishing, Ltd
- Местоположение издательства: Road Town, United Kingdom
- Первая страница: 510
- Последняя страница: 520
- DOI: 10.1134/S0006297917040137
- 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.
- Добавил в систему: Дорохов Юрий Леонидович
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