Chemotherapy is one of the major therapeutic options for cancer treatment. Chemotherapy is\noften associated with a low therapeutic window due to its poor specificity towards tumor cells/tissues.\nAntibody-drug conjugate (ADC) technology may provide a potentially new therapeutic solution for\ncancer treatment. ADC technology uses an antibody-mediated delivery of cytotoxic drugs to the\ntumors in a targeted manner, while sparing normal cells. Such a targeted approach can improve the\ntumor-to-normal tissue selectivity and specificity in chemotherapy. Considering its importance in\ncancer treatment, we aim to review recent efforts for the design and development of ADCs. ADCs are\nmainly composed of an antibody, a cytotoxic payload, and a linker, which can offer selectivity against\ntumors, anti-cancer activity, and stability in systemic circulation. Therefore, we have reviewed\nrecent updates and principal considerations behind ADC designs, which are not only based on the\nidentification of target antigen, cytotoxic drug, and linker, but also on the drug-linker chemistry\nand conjugation site at the antibody. Our review focuses on site-specific conjugation methods for\nproducing homogenous ADCs with constant drug-antibody ratio (DAR) in order to tackle several\ndrawbacks that exists in conventional conjugation methods.
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