Binding mechanisms of therapeutic antibodies to human CD20

Strength in numbers Human cluster of differentiation 20 (CD20) is expressed on malignant B cells and is the target of therapeutic antibodies used in cancer immunotherapy. Kumar et al. now present structures that explain why so-called type I antibodies efficiently activate the complement pathway to kill cells, whereas type II antibodies do not. Type I antibodies each bind to two CD20 dimers and form clusters that facilitate binding to a component of the complement pathway. The second-generation type I antibody ofatumumab has molecular features that make it more efficient at clustering than first-generation rituximab. By contrast, the type II antibody obinutuzumab interacts with just one CD20 dimer and cannot form higher-order assemblies. Understanding these mechanisms will inform the design of next-generation immunotherapies. Science , this issue p. 793