In oncology therapeutics, antibody-drug conjugates (ADCs) are becoming increasingly significant, with 14 ADCs approved for cancer treatment and more than 100 approved in global clinical trials. Traditional ADCs, produced through random conjugation to lysine or cysteine residues, often exhibit structural heterogeneity. This has led to a shift towards next-generation ADCs, which utilize specific conjugation chemistry for precise payload-linker attachment at designated antibody sites, aiming to enhance therapeutic indices . Affinity peptide-mediated chemical conjugation, which is becoming the standard method for site-specific ADC production, is typically challenged by peptide release and cleavage reagent removal (Figure ). The conjugation method developed by Zeng et al. in 2022, which utilizes optimized Fc-affinity peptides, marks a considerable advancement, notable for its single-step process . However, areas could still benefit from further refinement, such as the in vivo stability and developability of ADC. To ensure these qualities, additional pharmacokinetic studies are required to better understand the behavior of ADCs. In addition, the current method poses challenges for good manufacturing practices (GMP) ADC production. The synthesis of peptide reagents linked to the payload-linker is complex and raises concerns in the context of GMP, particularly given the necessity to minimize steps involving high-potency payloads for environmental, health, and safety reasons . This traceless affinity approach requires multiple steps that involve payload handling. Therefore, we advocate a simpler manufacturing process.