Stabilization of Antibody Drug Conjugate (ADC) products by lyophilization: a review

advances in linker chemistry and cytotoxic payloads have improved safety and efficacy.Extensive work resulted in the approval of ado-trastuzumab emtansine (Kadcyla) and brentuximab vedotin (Adcetris), which offered targeted treatments for HER2-positive breast cancer and Hodgkin lymphoma, respectively.Moreover, the recent approval of Enhertu greatly demonstrated clinically meaningful benefits for patients with HER2-positive breast cancer, and it's also the first approved tumoragnostic HER2-targeted treatment.Early antibody-drug conjugates (ADCs) faced some limitations such as non-specific conjugation methods, unstable linkers (e.g., hydrazone) etc. and instability during the circulation, which lead to heterogeneous mixtures with variable drug-to-antibody ratios (DARs) and unpredictable pharmacokinetics and inconsistent therapeutic outcomes (Colombo et al. 2024).To overcome these challenges, recent advances in site-specific conjugation technologies have transformed ADC design and performance (Palacino et al. 2022;Colombo et al. 2024).One key innovation is ThiomAb technology, which introduces engineered cysteine residues into the antibody structure, allowing precise and uniform drug attachment.