Cysteine-Based Coupling: Challenges and Solutions

Antibody-drug conjugates (ADCs) have attracted great attention in recent years in the wake of an accelerated FDA approval rate and several large-scale acquisitions. To date, there are ten ADC drugs on the market and more than 70 in various stages of clinical trials. Yet, due to the complicated nature of ADC molecules, considerations need to cover many aspects for the success of ADCs, including target specificity, linker-payload stability, tumor permeability, and clearance rate. This topical review summarizes and discusses current methods used to increase stability and homogeneity of ADCs of cysteine conjugation. We believe that they will lead to improvement of efficacy and pharmacokinetics (PK) of ADC drugs.

Automated summary

ADCs, a topic of great interest in recent years, have seen ten drugs on the market and over 70 in clinical trials. Success of ADCs relies on various factors such as target specificity and molecule stability. Methods discussed in this review for improving stability and homogeneity of cysteine-conjugated ADCs are expected to enhance drug efficacy and pharmacokinetics.