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• In the first generation of ADC drugs, anticancer drugs mainly bind to mouse monoclonal antibodies through non-degradable linkers.
• In the second generation of ADC drugs, monoclonal antibodies show increasing selectivity for tumor cells and decreasing cross-reactivity with normal cells. However, due to off-target toxicity, competition with unbound antibodies, and issues such as ADC aggregation or rapid clearance caused by a drug-to-antibody ratio (DAR) of 8, most second-generation ADCs currently exhibit a narrower therapeutic window.
• Optimizing monoclonal antibodies, linkers, and conjugation processes can improve the therapeutic index of third-generation ADCs. Site-specific conjugation is considered crucial for the successful development of ADCs, ensuring a defined DAR value and homogeneity of ADCs.
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