Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Autor: Jodie L. Abrahams, Radka Saldova, Rick Kapur, Agnes L. Hipgrave Ederveen, Natalia I. Olovnikova, Kathryn L. Armour, Manfred Wuhrer, Gestur Vidarsson, Belinda Kumpel, Carolien A. M. Koeleman, Pauline M. Rudd
Přispěvatelé: Ederveen, Agnes Hipgrave [0000-0003-1689-0442], Vidarsson, Gestur [0000-0001-5621-003X], Kapur, Rick [0000-0002-1608-876X], Wuhrer, Manfred [0000-0002-0814-4995], Apollo - University of Cambridge Repository, AII - Inflammatory diseases, AII - Cancer immunology, Landsteiner Laboratory
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports
Scientific Reports, 10(1). NATURE PUBLISHING GROUP
Scientific reports, 10(1):1464. Nature Publishing Group
Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
DOI: 10.1038/s41598-019-57393-9
Popis: Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in FcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADCC activity. In vivo, two B mAb-Ds with 77–81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with 60%) together with lower fucosylation (
Databáze: OpenAIRE