The Evolution of Antibody-Drug Conjugates: Toward Accurate DAR and Multi-specificity.

Autor: Dong W; State Key Laboratory of Elemento-Organic Chemistry and Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, China., Wang W; State Key Laboratory of Elemento-Organic Chemistry and Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, China., Cao C; State Key Laboratory of Elemento-Organic Chemistry and Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, China.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2024 Sep 02; Vol. 19 (17), pp. e202400109. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1002/cmdc.202400109
Abstrakt: Antibody-drug conjugates (ADCs) consist of antibodies, linkers and payloads. They offer targeted delivery of potent cytotoxic drugs to tumor cells, minimizing off-target effects. However, the therapeutic efficacy of ADCs is compromised by heterogeneity in the drug-to-antibody ratio (DAR), which impacts both cytotoxicity and pharmacokinetics (PK). Additionally, the emergence of drug resistance poses significant challenges to the clinical advancement of ADCs. To overcome these limitations, a variety of strategies have been developed, including the design of multi-specific drugs with accurate DAR. This review critically summarizes the current challenges faced by ADCs, categorizing key issues and evaluating various innovative solutions. We provide an in-depth analysis of the latest methodologies for achieving homogeneous DAR and explore design strategies for multi-specific drugs aimed at combating drug resistance. Our discussion offers a current perspective on the advancements made in refining ADC technologies, with an emphasis on enhancing therapeutic outcomes.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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