Anti-Human CD20 (Obinutuzumab) [Clone GA101] — Fc Muted™,Leinco,LT912

CD20 is a nonglycosylated 33-37 kDa phosphoprotein member of the MS4A family which is widely expressed on normal B cell surfaces during all stages of development as well as by most B cell malignancies 1,2 . The biological role of CD20 remains poorly understood; however, it is thought to be involved in calcium ion influx. CD20 has no natural ligand and is not immediately internalized upon antibody binding. Thus, mAbs directed against CD20 depend on the recruitment of a host response. Anti-CD20 mAbs bind to the 44 amino acid extracellular portion. Obinutuzumab (GA101) is a new generation, type II, anti-CD20 antibody 2 . Obinutuzumab was humanized by grafting the complementarity-determining sequences of murine IgG1-κ antibody B-Ly1 onto human VH and VL acceptor frameworks 3 . The Fc segment was glycoengineered to attach bisected, complex, nonfucosylated oligosaccharides to asparagine 297, leading to increased affinity to FcgRIII. Obinutuzumab causes homotypic adhesion 4,5,6 , induces direct cell death via largely caspase-independent mechanisms 4,6,7,8,9 , does not localize into lipid rafts 4,10,11 , displays half-maximal CD20 binding at saturating conditions 7 , and displays minimal complement dependent cytotoxicity 7 . Compared to rituximab, obinutuzumab recognizes a distinct but overlapping CD20 epitope, in a different orientation that results in increased pro-apoptotic potential 12,13,14 . A modified elbow-hinge residue, characterized by a leucine to valine mutation at Kabat position 11, is key to superior phosphatidylserine exposure and cell death relative to rituximab 3 .