Antibody Drug Conjugates - An alternative delivery system for chemotherapeutic payloads : nonclinical challenges and considerations

抄録

Antibody drug conjugates have been hailed as a step change in the goal to specifically and safely, deliver highly toxic chemotherapeutic agents, and by so doing, increase their anti-tumour efficacy while reducing dose limiting toxicity. Despite a number of successful regulatory approvals and impactful clinical outcomes for cancer patients, developing a successful ADC is still challenging. The different classes of cytotoxic warheads employed in ADCs have overlapping and unique dose limiting toxicities in the clinic, that are not always predicted by non-clinical toxicology studies. This presentation will cover some of the key aspects that impact the pre-clinical development of ADCs, outline how the same factors that drive efficacy, such as antibody-specificity, linker-composition and payload-specific mode of action pharmacology, also drive the toxicity of the ADC. A case example of the development path of an ADC will be shared with emphasis on the challenges faced by the toxicologist to deliver a well characterised risk assessment for the clinic.