Advances in Site-specific Conjugation Technologies Applied to the Synthesis of Antibody-Drug Conjugates
Antibody-drug conjugates(ADCs),as an emerging therapy for cancer treatment,have made significant progress in the past few decades.However,due to the heterogeneity of ADCs,they still face various issues and challenges in clinical therapy.Therefore,site-specific conjugation techniques have become a crucial area of research in ADCs,and in recent years,this field has witnessed numerous breakthrough advancements,empowering ADCs with enhanced performance.The review provides a comprehensive overview of the frontiers in site-specific conjugation technologies for ADCs.Categorized into seven major classes including lysine-based,cysteine-based,low-abundance amino acid-based and glycosylation site-based conjugation techniques,ribosomal incorporation of unnatural and noncanonical amino acids and enzyme-mediated conjugation techniques,it meticulously describes 21 classical and emerging techniques such as the THIOMAB technology and linchpin-directed modification,in order to offer valuable insights for the development of next-generation ADCs.
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