Probing the Internalization and Efficacy of Antibody‐Drug Conjugate via Site‐Specific Fc‐Glycan Labelling of a Homogeneous Antibody Targeting SSEA‐4 Bearing Tumors

Antibody drug conjugates (ADC) are an emerging class of pharmaceuticals consisting cytotoxic agents covalently attached to antibody designed target a specific cancer cell surface molecule followed by internalization and intracellular release payload exhibit its anticancer activity. Targeted delivery variety cells has been demonstrated have significant enhancement in clinical efficacy dramatic reduction off-target toxicity. Site-specific conjugation the is highly desirable for development ADC with well-defined antibody-to-drug ratio, enhanced internalization, reduced toxicity, improved stability, desired pharmacological profile optimal therapeutic index. Here, we reported site-specific strategy evaluation SSEA4 on solid tumors. This stems from azido-fucose tag homogeneous Fc-glycan generated via vitro glycoengineering approach optimization antibody-drug ratio efficacy. The chimeric anti-SSEA4 chMC813-70, conjugated antineoplastic agent monomethyl auristatin E both cleavable non-cleavable linkers showed excellent cytotoxicity towards SSEA4-bearing cells. A clear distinction was observed among different expression levels.