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ADC & Payloads Science

Antibody Drug Conjugates (ADC) are composed of a monoclonal antibody targeting a tumoral cell receptor, a linker and a toxic payload.

ADCs are only successful if each component is effective. The monoclonal antibody guides the toxic payload selectively to the tumor cell. The antibody needs to bind preferentially to malignant cells at a relatively high density, and internalize in a way that allows the release of the drug from the linker in the appropriate intracellular compartment.

The linker securely attachs the drug to the antibody to assure a stability in the circulation, and releases the drug once it is internalized. The cytotoxic drug needs to be nontoxic when linked to the mAb in the circulation, but capable of killing tumor cells once it is internalized and released. The conjugation of the cytotoxic molecule to the antibody inactivates the drug while it is in circulation.

Like a Trojan horse, the toxin enters the cancer cell unnoticed in this way. At this point, the toxin is still firmly connected with the antibody. This connection must be broken before the active substance can begin its deadly work within the tumor. The linker provides cleavage and release of the toxin within the targeted cancer cell leading to cell death. Efficient internalization of the antigen is one of the key points if this mechanism of action.