ADC Linkers

Linkers usually include four parts: antibody linker, regulatory fragment, enzyme degradation fragment, self-cleavage fragment, and covalently link antibodies and payloads. Appropriate linker design can optimize drug structure, improve ADC solubility and PK, increase cleavage efficiency, enhance ADC activity, etc. The hydrolysis of linkers in cells can be roughly divided into two categories: cleavable and non-cleavable. Cleavable linkers contain chemical triggers, which can release payloads after cleavage and are highly flexible. The released payload can diffuse into surrounding cells and exert a bystander effect. Non-cleavable linkers do not contain chemical triggers and cannot exert a bystander effect, so they are mainly used for hematological tumors and tumors with high antigen expression. In addition, their off-target toxicity is small, but they may produce drug resistance.