Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling
Document title: Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling
Journal: Electronic journal of biotechnology
Database: PERIÓDICA
System number: 000358910
ISSN: 0717-3458
Authors: 1
1
2
3
2
1
Institutions: 1Polymaris Biotechnology, Morlaix Chamber of Commerce and Industry, Morlaix. Francia
2IFREMER-Brest Center, Biotechnologies and Marine Molecules laboratory, Brest, Finistere. Francia
3Brest University Hospital, Cellular Therapy and Immunobiology of Cancer laboratory, Brest, Finistere. Francia
Year:
Volumen: 15
Number: 5
Country: Chile
Language: Inglés
Document type: Artículo
Approach: Experimental, analítico
English abstract 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
Disciplines: Medicina,
Biología
Keyword: Terapéutica y rehabilitación,
Inmunología,
Inmunoterapia,
Anticuerpos monoclonales,
Biotecnología,
Citotoxicidad,
Oligosacáridos,
Linfoma,
Xenoantígenos,
Linfoma no Hodgkin
Keyword: Medicine,
Biology,
Therapeutics and rehabilitation,
Immunology,
Immunotherapy,
Monoclonal antibodies,
Biotechnology,
Cytotoxicity,
Oligosaccharides,
Non-Hodgkin lymphoma,
Xenoantigens,
Lymphoma
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