Antibody-drug conjugates (ADCs) are one of the most rapidly expanding forms of oncology treatment and therapeutic successes have led to an unprecedented expansion in the number of ADCs in development,1 with over 200 currently in clinical trials.
While ADCs represent an exciting new advance, the attrition rates for potential drug candidates remain particularly high at every stage of development. Additionally, progress has been far from linear,2 with several ADCs gaining approval only to be withdrawn and then reapproved. One of the reasons for this is the complexity of these therapeutics,3 both in terms of their multiple components and their complicated, multi-step mechanisms of action.
To overcome these challenges and maximise the potential of this promising new drug class, sophisticated preclinical testing platforms are essential.4 In recent years, organoids and patient-derived xenograft (PDX) models have emerged as the gold standards5 of ADC development. Each model type offers distinct advantages and limitations, which can be leveraged or mitigated by using the most appropriate models during different preclinical stages. Understanding how to effectively utilise these models together is foundational to the successful development of ADCs.
Utilising Organoids in ADC Development
Organoids are three-dimensional cellular structures that retain the form and function of tumour structures. Recent advances in organoid technology have been shown to support more complex, rigorous and informative validation of ADC performance6 ahead of larger, more expensive clinical trials. Organoids are particularly appropriate for:
