Table 2.

Summary of endocytosis activities for the receptors for the currently approved ADCs.

Receptor	Pathway	Activity	Association with ADC Efficacy/Resistance
CD33	CME	Poor	● AML patients who do not respond to GO have been linked to poor receptor internalization
CD30	CME	Poor	● Undergoes significant shedding from cell surface
CD22	CME	Good	● Fast endocytosis activates intracellular pools, which replenish the level of CD22 expression
CD79b	CME	Good	● Due to rapid internalization and trafficking to lysosomes, patients will most likely respond to PV treatment
Trop2	CME	Good	● Strong preclinical data link internalization to efficacy
BCMA	Insufficient information	Good	● Insufficient information
HER2	Clathrin-independent (caveolae +/−)	Poor	● Poor internalization linked with poor clinical outcomes ● Dysregulation of the endocytotic machinery has been linked to resistance in preclinical models ● Novel strategies such as induced HER2 crosslinking to improve endocytosis are currently in clinical testing
Nectin-4	Macropinocytosis	Good	● Insufficient information