Antibody-Drug Conjugates (ADCs) are a class of targeted drugs composed of a drug linked to an mAbs (antibody) that is designed to specifically release their payload at a tumor.
When designed ADCs there are several features of the cancer and the compound that needs to be concerned: choosing monoclonal antibodies based on a certain type of tumor-associated antigen, linkers, and payloads. Figure 1 illustrates the considerations for ADC development.
The antibodies are selected for their binding to specific antigens that are generally more numerous on the surface of cancer cells than healthy cells.
The linkers holding the cytotoxic drug to the antibody needs to be resilient enough to stay together during the journey to the tumor while not inhibiting the payload once inside the cell.
The active payload may act by either microtubule inhibition or DNA damage/entanglement. The inherent potency of the released drug must be sufficient to kill the tumor cells at a low concentration.
This means that very potent drugs with sub-nanomolar IC50 are typically used that are 100-1000-fold more potent than traditional anticancer agents. This type of targeting with small quantities of highly potent payloads is designed to limit side effects and provide a wider therapeutic window than other chemotherapeutic agents.
Figure 2 shows the 6 steps that occur with ADC drugs once they are inserted into a patient's body as well the potential problems that must be addressed in designing an ADC drug.
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