Considerations of toxicologic pathology examination of antibody-drug conjugates during nonclinical safety evaluation
Antibody-drug conjugate drug(ADC)are novel specific anti-tumor drugs composed of antibodies,payloads(cytotoxic small molecule compounds)and linkers.ADC is characterized by high specificity and few side effects,but their safety is affected by factors such as antibody specificity,stability of linker,and nature of payload.The dose-limiting toxicity of ADC is mainly related to the payload and has been well correlated in clinical and nonclinical studies.The toxicity mechanism of ADC includes on-target toxicity and off-target toxicity.On-target toxicity is mainly determined by the expression of the target,whereas off-target toxicity is caused by factors such as coupling instability and non-specific uptake.The toxicity mechanism of ADC is briefly reviewed,and the toxicologic pathology examination during nonclinical safety evaluation of ADC is emphasized,so as to provide some references for the nonclinical safety evaluation of ADC in China.
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