Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling
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...
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Pontificia Universidad Católica de Valparaíso
2012
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oai:scielo:S0717-345820120005000052012-11-29Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan couplingCourtois,AnthonyGac-Breton,StéphanieBerthou,ChristianGuézennec,JeanBordron,AnneBoisset,Claire complement system Gala(1→3)Gal epitope immunogenic oligosaccharide immunotherapy non-Hodgkin lymphoma xenoantigen 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 Galα(1→3)Galβ(1→4)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the α-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.info:eu-repo/semantics/openAccessPontificia Universidad Católica de ValparaísoElectronic Journal of Biotechnology v.15 n.5 20122012-09-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582012000500005en |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
complement system Gala(1→3)Gal epitope immunogenic oligosaccharide immunotherapy non-Hodgkin lymphoma xenoantigen |
| spellingShingle |
complement system Gala(1→3)Gal epitope immunogenic oligosaccharide immunotherapy non-Hodgkin lymphoma xenoantigen Courtois,Anthony Gac-Breton,Stéphanie Berthou,Christian Guézennec,Jean Bordron,Anne Boisset,Claire Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| description |
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 Galα(1→3)Galβ(1→4)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the α-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. |
| author |
Courtois,Anthony Gac-Breton,Stéphanie Berthou,Christian Guézennec,Jean Bordron,Anne Boisset,Claire |
| author_facet |
Courtois,Anthony Gac-Breton,Stéphanie Berthou,Christian Guézennec,Jean Bordron,Anne Boisset,Claire |
| author_sort |
Courtois,Anthony |
| title |
Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| title_short |
Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| title_full |
Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| title_fullStr |
Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| title_full_unstemmed |
Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| title_sort |
complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling |
| publisher |
Pontificia Universidad Católica de Valparaíso |
| publishDate |
2012 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582012000500005 |
| work_keys_str_mv |
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| _version_ |
1718441860266983424 |