Sunbae Lee

Poster Abstract (2013 World ADC Summit, Frankfurt) Site-specific conjugation at the heavy chain C-terminus of Herceptin variant in the development of antibody-drug conjugate Hye-Shin Chung, 1, Sun-Bae Lee 2, Yong-Mo Kim 2, and Soon Jae Park 2 1. Dept of Biotechnology, Han Nam University, Jeon Min Dong, Yu Sung Gu, Dae Jeon, Korea 2. Alteogen Inc., Bioventure Town, Jeon Min Dong, Yu Sung Gu, Dae Jeon, Korea Controlling the conjugation sites and the number of drugs are one of the major issues in the development of antibody-drug conjugates. We introduced a peptide motif containing cysteine residues at the C-terminus of Herceptin heavy chain for the site-specific conjugation of drugs and the conjugation efficiency was achieved around 70~90% without detectable non-specific conjugation of the drugs at the other sites of the antibody. Peptide mapping result of a drug-conjugated Herceptin variant indicated that drugs were conjugated site-specifically at the intended conjugation site. Drug-conjugated Herceptin showed a significant cytotoxicity against SK-BR-3 breast cancer cell with IC50 of about 120 pM. Caspase activity assay also indicated that cell death was due to apoptosis by the Herceptin-attached drug. Her2 binding assay revealed that drug conjugation at C-terminus of Herceptin heavy chain did not disturb the antigen binding efficacy. These results indicated that the C-terminus of the heavy chain of an antibody could be a highly effective and specific conjugation target site without disturbing antibody functionality.