After nearly three decades of development and three rounds of technological iteration, antibody-drug conjugates (ADCs) have become a mainstream class of anti-tumor therapeutics due to their high efficacy and favorable safety profile.
However, ADCs represented by Enhertu, which utilize thiol-based conjugation and high payloads, still exhibit on-target toxicities such as hematologic toxicity and interstitial lung disease. These side effects are largely attributable to premature payload shedding and the instability inherent in high drug-to-antibody ratios (DARs) characteristic of thiol-based conjugation.
Through advanced cell engineering and precise process control, we obtain homogeneous antibody Fc glycan structures. Building on this glycan foundation, we have developed a one-enzyme, two-step process to generate highly homogeneous DAR4 conjugates. Subsequently, by leveraging distinct glycan structures, we have also established a one-step transfer method for DAR2 conjugation. Glycan-specific conjugated ADCs exhibit superior hydrophilicity, serum stability, and pharmacokinetic properties, significantly enhancing their safety profile.
