Method of Producing Human IgG Antibodies with Enhanced Effector Functions

摘要

A method for generating human IgG₁ antibodies with enhanced Fc effector function is disclosed. In practicing the method, an IgG₁ Fc look-through mutagenesis (LTM) coding library directed at four receptor-contact regions of the Fc C_H2 portion of in human IgG₁ Fc is expressed in a system in which the mutated Fc fragments are displayed on the surfaces of the expression cells. The fragments are then screened for altered binding affinity to a selected Fc receptor or other Fc-binding protein. The selected mutations may be used, in turn, to guide the selection of multiple substitutions in the construction of a walk-through mutation (WTM) library, for generating additional Fc fragment mutations with desired binding properties. The antibodies so produced have a variety of therapeutic and diagnostic applications.