Gewählte Publikation:
Strasser, R; Castilho, A; Stadlmann, J; Kunert, R; Quendler, H; Gattinger, P; Jez, J; Rademacher, T; Altmann, F; Mach, L; Steinkellner, H.
(2009):
Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous beta1,4-galactosylated N-glycan profile.
J Biol Chem. 2009; 284(31):20479-20485
FullText
FullText_BOKU
- Abstract:
- It is well established that proper N-glycosylation significantly influences the efficacy of monoclonal antibodies (mAbs). However, the specific immunological relevance of individual mAb-associated N-glycan structures is currently largely unknown, because of the heterogeneous N-glycan profiles of mAbs when produced in mammalian cells. Here we report on the generation of a plant-based expression platform allowing the efficient production of mAbs with a homogeneous beta 1,4-galactosylated N-glycosylation structure, the major N-glycan species present on serum IgG. This was achieved by the expression of a highly active modified version of the human beta 1,4-galactosyl-transferase in glycoengineered plants lacking plant-specific glycosylation. Moreover, we demonstrate that two anti-human immunodeficiency virus mAbs with fully beta 1,4-galactosylated N-glycans display improved virus neutralization potency when compared with other glycoforms produced in plants and Chinese hamster ovary cells. These findings indicate that mAbs containing such homogeneous N-glycan structures should display improved in vivo activities. Our system, using expression of mAbs in tobacco plants engineered for post-translational protein processing, provides a new means of overcoming the two hurdles that limit the therapeutic use of anti-human immunodeficiency virus mAbs in global health initiatives, low biological potency and high production costs.
- Autor*innen der BOKU Wien:
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Altmann Friedrich
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De Vitoria Pereira Alexandra
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Gattinger Pia Simone
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Kunert Renate
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Mach Lukas
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Quendler Heribert
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Stadlmann Johannes
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Steinkellner Herta
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Strasser Richard
- BOKU Gendermonitor:
- Find related publications in this database (using NML MeSH Indexing)
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Animals -
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Antibodies, Monoclonal - biosynthesis
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CHO Cells -
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Cell Line -
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Cricetinae -
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Cricetulus -
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Crosses, Genetic -
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Galactose - metabolism
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Genetic Vectors - genetics
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Glycosylation -
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HIV Antibodies - biosynthesis
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HIV-1 - immunology
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Humans -
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Mutation - genetics
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Neutralization Tests -
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Plantibodies - immunology
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Polysaccharides - metabolism
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Protein Isoforms - chemistry
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Rats -
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Tobacco - genetics
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Transformation, Genetic -
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