03.06 Understanding how epitope binding influences antibody dependent complement engagement for therapy of B-cell malignancies

• DOI: 10.1136/jitc-2022-itoc9.2
• Publication Date: 2022-09-22T00:30:36Z
• Authors: S Bondza; J Buijs; A Lux
• Keywords: Ofatumumab; Obinutuzumab; Complement-dependent cytotoxicity; Raji cell

<h3>Background</h3> Monoclonal antibodies (mAbs) have the capacity to combine targeted therapy with immune activation through recruitment of cells and complement proteins via their Fc-terminus. For treatment B-cell malignancies, mAbs targeting surface marker CD20 are well established; Rituximab, Ofatumumab Obinutuzumab being most commonly used in clinic. Even though these three all IgG1 subclass they differ effector functions, especially ability engage system for depletion. Efforts been made relate functional properties molecular characteristics allow informed decisions when designing next generation therapeutics. <h3>Materials Methods</h3> Real-time interaction analysis was performed LigandTracer deduct binding mechanism protein on live cell lines primary B-cells. Efficiency dependent killing evaluated <i>in vitro</i>. <h3>Results</h3> displayed stable driven by bivalent target engagement which independent antibody concentration. Rituximab could overall more compared Obinutuzumab, but both antibodies, stabilization due bivalency decreased increasing concentration, resulting dose-dependent apparent affinities. The strength first component C1q Fc-terminus cell-bound correlated positively degree CD20. Kinetic revealed two multivalent components that represent low- high-order IgG Fc-oligomers surface. latter characterized capture dominant Ofatumumab. Target efficient strong high stability. <h3>Conclusions</h3> Taken together this implies helps cluster leading beneficial arrangement Fc optimization avidity effects, translates cascade. These findings strongly supported recent structural data field add understanding how influences mAbs. <h3>Disclosure Information</h3> <b>S. Bondza:</b> A. Employment (full or part-time); Significant; Ridgeview Instruments. <b>J. Buijs:</b> <b>A. Lux:</b> None.