Antibody drug conjugates (ADCs) are a new class of therapeutics that combine monoclonal antibodies with chemotherapy drugs. The objective of an ADC is to deliver cytotoxic chemotherapy drugs directly and specifically to cancer cells while sparing normal tissues. ADCs work by using monoclonal antibodies to target cell-surface antigens that are specifically expressed on cancer cells. These antibodies are then chemically linked to active anti-cancer agents or drugs. When ADCs bind to the antigen on cancer cells, they are internalized into the cells through receptor-mediated endocytosis followed by release of the bioactive anti-cancer drug. This initiates cell death in these targeted cancer cells while minimizing effects on non-targeted cells.

Mechanism of Action of ADCs

As mentioned earlier, Antibody Drug Conjugates  work by taking advantage of the target specificity of monoclonal antibodies and the killing power of chemotherapy drugs. The 3 main components of an ADC are:

1. Monoclonal Antibody (mAb): The mAb component binds specifically to a cell surface antigen that is uniquely or highly expressed on cancer cells. This ensures the ADC is delivered directly to the tumor.

2. Linker: The linker attaches the cytotoxic drug to the mAb. It is designed to break down inside cancer cells, releasing the drug. Lysosomal protease activity triggers the release of drug from the linker.

3. Cytotoxic Drug (Payload): The anti-cancer drug is conjugated to the mAb via the linker. Examples include microtubule inhibitors like auristatins and maytansinoids which prevent cell division. The released drug leads to cell cycle arrest and apoptosis of cancer cells.

After binding to the target antigen on cancer cells, the ADC is internalized through receptor-mediated endocytosis. Inside the cell, enzymatic cleavage of the linker releases the cytotoxic drug. The unconjugated antibody is degraded or recycled while the freed drug induces cancer cell death. This ensures minimal exposure of normal tissues to the toxin.

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