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(A) Fate of an ADC before and after internalization. Premature cleavage of the linker in extracellular matrix is often associated with off-target toxicity. Antigen-mediated endocytosis delivers ADC in the endosomal–lysosomal system and lysosomal linker cleavage releases the drug, which acts to exert its cytotoxicity. (B) Effect of amino acid composition in the linker peptide and substitution on the benzene ring of PABC on linker stability in mouse plasma.
