New insights in Type I and II CD20 antibody mechanisms-of-action with a panel of novel CD20 antibodies

British Journal of Haematology
Saskia MeyerJeanette H W Leusen

Abstract

Based on their mechanisms-of-action, CD20 monoclonal antibodies (mAbs) are grouped into Type I [complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC)] and Type II [programmed cell death (PCD) and ADCC] mAbs. We generated 17 new hybridomas producing CD20 mAbs of different isotypes and determined unique heavy and light chain sequence pairs for 13 of them. We studied their epitope binding, binding kinetics and structural properties and investigated their predictive value for effector functions, i.e. PCD, CDC and ADCC. Peptide mapping and CD20 mutant screens revealed that 10 out of these 11 new mAbs have an overlapping epitope with the prototypic Type I mAb rituximab, albeit that distinct amino acids of the CD20 molecule contributed differently. Binding kinetics did not correlate with the striking differences in CDC activity among the mIgG2c mAbs. Interestingly, chimerization of mAb m1 resulted in a mAb displaying both Type I and II characteristics. PCD induction was lost upon introduction of a mutation in the framework of the heavy chain affecting the elbow angle, supporting that structural changes within this region can affect functional activities of CD20 mAbs. Together, these new CD20 ...Continue Reading

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Citations

Apr 28, 2019·Expert Opinion on Biological Therapy·Mihai AncauBernhard Hemmer
Apr 11, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mitchell EversJeanette H W Leusen
Apr 30, 2019·Frontiers in Immunology·Arianne M BrandsmaToine Ten Broeke
Feb 8, 2018·British Journal of Haematology·Grzegorz StasiłojćMarcin Okrój
Jul 12, 2019·Frontiers in Immunology·Dario DidonaMichael Hertl
Apr 22, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Esther S FrischMartin S Weber
May 26, 2021·MAbs·Monica L Fernández-QuinteroKlaus R Liedl
Jul 4, 2021·Rheumatic Diseases Clinics of North America·Susan P Canny, Shaun W Jackson
Jun 25, 2021·Frontiers in Molecular Biosciences·Nathaniel L MillerRam Sasisekharan
Jul 11, 2021·Indian Journal of Dermatology, Venereology and Leprology·Anuradha BishnoiRahul Mahajan
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·M Tommy GamblesJindřich Kopeček
Aug 11, 2021·Expert Opinion on Emerging Drugs·Jennifer L Crombie, Jennifer R Brown
Aug 13, 2021·Journal of Neurology·Monica MargoniMaria A Rocca
Jun 20, 2021·Cancer Research·Li-Chung TsaoZachary C Hartman

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