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The Selection Of Antibody And Linker Of Antibody-Drug Conjugates

The Selection Of Antibody And Linker Of Antibody-Drug Conjugates

The antibodies in ADC are used to precisely target cells for antibody compounds that are highly cytotoxic. Optimizing antibodies can also drastically reduce the binding of non-specific ADCs and prolong the half-life of ADCs in the blood.

In early studies, the use of mouse antibodies by antibody & Elisa experts often resulted in a severe immune response and patients developed anti-mouse antibodies that significantly reduced the therapeutic effect. In recent years, with breakthroughs in antibody technology, it has become possible to use human antibodies or all human antibodies as the main component in ADC. The most commonly used form of antibody is the IgG family, specifically IgG1. 

Antibodies as a component of ADC retain their original qualities in the body and activate immune functions such as antibody-dependent cellular cytotoxicity (ADCC) and complementary cytotoxicity. In addition, some antibodies also have receptor blockers or signalling pathways. These independent antibody activities are not always useful or complementary to ADCs, while others can cause increased toxicity to the body and attenuate tumour tissue targets and ADC drug internalization.

Linker options

The linker helps bind antibodies and chemical drugs, which directly influence the ADC's pharmacokinetics, therapeutic index and therapeutic effect.

The drug-conjugated antibody interface must have the following properties: Stability without releasing the cytotoxic drug molecule before it reaches a predetermined target, resulting in non-target toxicity. If the target site is endogenous, drug molecules can be released quickly and efficiently.