RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse eventsThe development of ADCs sfaces challenges. Certain types of cancer lack effective neoantigens. For instance, the discovery and validation of neoantigens are time-consuming, and the expression of antigens varies among individuals. Additionally, tumors may alter the expression of their surface antigens to evade the immune system’s attack, which can make it difficult to identify suitable antibodies. Furthermore, ADCs undergo complex metabolic processes. Due to their diverse designs, ADCs lack uniform metabolic properties. Even ADCs targeting the same antigen may exhibit differences in plasma stability, in vivo metabolism, PK/PD relationships, and adverse reactions owing to variations in antigen epitope recognition, linker sites, coupling chemistry, and the choice of small molecule toxins. Additionally, ADCs still have toxicities, such as on-target/off-tumor toxicity and off-target/off-tumor toxicity, with the latter being caused by the premature release of toxins into the bloodstream, non-tumor tissues, or the tumor microenvironment. Furthermore, the mechanisms of ADC resistance have not been thoroughly studied, and the production and quality control of ADCs also pose difficulties, all of which affect the production and clinical application of ADC drugs.