Complement-Dependent Activity of CD20-Specific IgG Correlates With Bivalent Antigen Binding and C1q Binding Strength

Monoclonal antibodies directed against the CD20 surface antigen on B cells are widely used in therapy of cell malignancies. Upon administration, bind to expressing and induce their depletion via cell- complement-dependent cytotoxicity or by induction direct killing. The three currently most often clinic Rituximab (RTX), Ofatumumab (OFA) Obinutuzumab (OBI). Even though these all human IgG1 subclass, they have previously been described vary considerably effector functions involved therapeutic depletion, especially regards complement activation. Whereas OFA is known strongly cytotoxicity, OBI be far less efficient. In contrast, role RTX-induced still under debate. Some this dissent might come from use different vitro systems for characterization antibody functions. We therefore set out systematically compare as well C1q binding complement-activation RTX, lines that differ expression levels complement-regulatory proteins primary cells. Applying real-time interaction analysis, we show overall strength live target coated with positively correlated degree bivalent CD20. Kinetic analysis revealed exhibits two modes distinct affinities stabilities, exact numbers varying both between lines. Furthermore, killing RTX was highly cell-line dependent, whereas superior independent All were able initiate deposition C3b surface, although extent. This suggests activation occurs but not necessarily lead cytotoxicity. could, however, phagocytosis an alternative mechanism depletion.