AJICAP Second-generation: Realizing Versatility and Robustness through Fc-Affinity Guided Chemical Conjugation Technology

Abstract

Over the past decade, site-specific chemical conjugation has emerged as a promising strategy to produce antibody-drug conjugates (ADCs) in the field of oncology [1]. Daiichi-Sankyo’s chemical conjugation method, which uses high drug-to-antibody ratio (DAR) technology, was approved by the U.S. Food and Drug Administration as the first site-specific ADC (fam-trastuzumab-deruxtecan-nxki; Enhertu® | Daiichi Sankyo and AstraZeneca). However, owing to limitations in high-DAR technology and the potential need for DAR=2 production, the Ajinomoto group has been developing a chemical site-specific conjugation technology using Fc-affinity peptide reagents since 2019 [2]. This approach modifies a specific lysine in the Fc region of various antibodies such as IgG1, IgG2, and IgG4 to create homogeneous DAR=2 ADCs, as demonstrated in a proof-of-concept study.