Research Progress on Mechanisms and Optimization Methods for Toxicity Induced by Antibody-Drug Conjugates

VernacularTitle:抗体-药物偶联物毒性的发生机制与优化方法研究进展
Author: Yanli JIA ¹ ; Xiaoyu LI ; Houwu FAN ; Wenqing DUAN ; Lixia HU ; Jian ZHOU ; Fengming RAN ; Shuang DONG
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1. 445600 恩施,咸丰县人民医院肿瘤科
Keywords: Antibody-drug conjugates; Targeted therapy; Toxicity; Optimization strategies
From: Cancer Research on Prevention and Treatment 2024;51(7):606-612
CountryChina
Language:Chinese
Abstract: Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.