Treatment of late stage solid tumors remain a major unmet medical need. Current therapeutic strategies are focused on developing inhibitors targeting mutated driving pathways or immune checkpoints. However, drug resistance and low response rate are limiting the long term success of these approaches.
Antibody–drug conjugates (ADCs) are monoclonal antibodies (mAbs) that are covalently linked to cell-killing drugs (payloads) (Figure). This approach combines the high specificity of mAbs against their antigen targets with highly potent cytotoxic drugs, which is too toxic for use as free drug in conventional chemotherapy. Such “Armed” mAbs can directly deliver the payload to antigen-enriched tumor cells and minimize systemic toxicity. Therefore, targeted delivery of highly potent cytotoxic drug increases both the efficacy and safety of therapy.
Figure. A schematic diagram illustrating the working principles of ADC. Upon binding to its target antigen, the mAb-antigen complex is internalized into endosomes which is then fused with lysosomes where the mAb is degraded and the drug is released.