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HKT288 is a first-in-class antibody-drug conjugate (ADC) targeting cadherin-6 (CDH6), a tumor-associated antigen overexpressed in certain solid tumors such as ovarian and renal cancers. The drug consists of a fully human monoclonal IgG1/κ antibody directed against CDH6, conjugated to a maytansine-based cytotoxic agent via an optimized linker. Upon binding to CDH6-expressing tumor cells, the ADC is internalized and releases its cytotoxic payload intracellularly, leading to inhibition of tubulin polymerization and subsequent cell cycle arrest and apoptosis. Preclinical studies demonstrated antitumor activity in ovarian and renal cancer models. Clinical development was terminated early due to unexpected neurotoxicity observed in phase I trials[1][2][3][4][5][6].
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