Antibody-conjugated drugs (antibody-drug conjugate,ADC) combine high specificity of monoclonal antibody drugs and high activity of small molecule cytotoxic agents to improve the targeting of tumor drugs and reduce toxic side effects.Compared to conventional complete or partially humanized antibodies or antibody fragments, ADC is theoretically more effective because it releases highly active cytotoxins within the tumor tissue.It has a higher tolerance or lower side effects compared to the fusion protein.The accurate identification of ADC drugs and the non-impact of cancer cells greatly improved the efficacy and reduced toxic side effects.Ideally, the drug precursor is not toxic upon systemic administration, and when antibodies in the ADC drug bind to target cells expressing the tumor antigen and the entire ADC drug is endocytoxed by tumor cells, the small molecule cytotoxin fraction will be released in sufficient efficiently active form to kill tumor cells.
The ADC is typically composed of a fully humanized monoclonal antibody (mAb), a cytotoxic drug, an appropriate linker, and an antigen specifically expressed on the tumor cells.The structure mainly maintains drug cytotoxicity, targeting and stability of ADC in the systemic circulation.The correct choice combination is key to the successful development of ADC.The targeting of ADCs drugs comes from the antibody fraction (antibody), the toxicity is mostly from the small molecular drug poison fraction (payload), and the antibody fraction can also have its own toxicity (ADCC with CDC).Antibodies are partially linked with the toxin partially via a linker (linker).After the antibody partially binds to a targeted antigen (binding on the surface of tumor cells), tumor cells endocytosis ADC (endocytosis).Later ADC drugs will break down in lysosomes (lysosomal degradation) to release active chemical poisons, disrupt DNA or prevent tumor cell division and act as killing cells.Idealized linkers should remain stable so do not lead to off-target toxicity (off-target toxicity) and have efficient release of poisons within the cell.
