Selecting an Optimal Antibody for AntibodyDrug Conjugate Therapy: Internalization and Intracellular Localization
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Antibody–drug conjugates (ADCs) combine the selectivity of a monoclonal antibody with the killing potency of a cytotoxic drug. For an antibody to function as a successful component of an ADC, it needs to bind to the target antigen on the surface of tumor cells and then be internalized by the cell. Following internalization, the ADC has to be transported to the lysosome where subsequent intracellular processing of the ADC will release the biologically active drug to exert its cytotoxic effects on tumor cells. This chapter describes some of the techniques that are currently used to determine internalization and proper intracellular trafficking of antibodies in order to select an optimal antibody for ADC therapeutics.