Drug-Linker Conjugates for Antibody Drug Conjugates (ADC) comprise of an active cytotoxic drug and an appropriate linker. The Drug-Linker Conjugates can expand the utility of monoclonal antibody (mAbs) and improve their potency and effectiveness. The site-specific conjugations of Drug-Linker to an antibody may involve genetic engineering of the mAb to introduce discrete, available cysteines or non-natural amino acids with an orthogonally-reactive functional group handle. These site-specific approaches not only increase the homogeneity of ADCs but also enable novel bio-orthogonal chemistries that utilize reactive moieties other than thiol or amine. The cytotoxic drug, monomethyl auristatin E (MMAE), is conjugated to the three trastuzumab variants using a protease cleavable linker and shows in vivo therapeutic efficacy.