| Registro completo |
| Provedor de dados: |
ArchiMer
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| País: |
France
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| Título: |
Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling
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| Autores: |
Courtois, Anthony
Gac Breton, Stephanie
Berthou, Christian
Guezennec, Jean
Bordron, Anne
Boisset, Claire
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| Data: |
2012-09
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| Ano: |
2012
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| Palavras-chave: |
Complement system Gal alpha(1 ->
3)Gal epitope immunogenic oligosaccharide immunotherapy non-Hodgkin lymphoma xenoantigen
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| Resumo: |
Oligosaccharides are implicated in the development of the immune response notably in complement activation. Anti-tumoural immunotherapy by monoclonal antibodies (mAbs) offers some advantages to chemotherapy including cell targeting but some of them are inefficient to generate cytotoxicity dependent complement (CDC) known to be important in the antibody's efficacy. The aim of this study is to give a CDC activity of mAb by linkage of a complement activating oligosaccharide to this antibody via a hetero-bifunctional linker allowing control of the conjugation reaction. We worked on non Hodgkin Burkitt's lymphoma as cancer source, Fab fragments of rituximab devoid of complement activity as mAb and the trisaccharide Gal alpha(1 -> 3)Gal beta(1 -> 4)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the alpha-Gal epitope was recognized by seric immunoglobulins. After checking the recognition capacity of the Fab-Gal conjugate for the CD20 epitope, in vitro assays were performed to evaluate the activation of the complement cascade by the Fab-Gal conjugate. The effect of this bioconjugate was confirmed by the evaluation of the proliferation response of Burkitt's cell line. The relative facility realization of this strategy represents new approaches to increase activities of mAbs.
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| Tipo: |
Text
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| Idioma: |
Inglês
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| Identificador: |
http://archimer.ifremer.fr/doc/00125/23599/21423.pdf
DOI:10.2225/vol15-issue5-fulltext-3
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| Editor: |
Univ Catolica De Valparaiso
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| Relação: |
http://archimer.ifremer.fr/doc/00125/23599/
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| Formato: |
application/pdf
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| Fonte: |
Electronic Journal Of Biotechnology (0717-3458) (Univ Catolica De Valparaiso), 2012-09 , Vol. 15 , N. 5 , P. 1-11
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| Direitos: |
2012 by Pontificia Universidad Católica de Valparaíso, Chile
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