Chuan-Lung Hsu
Development Center for Biotechnology, Taiwan
Title: A novel versatile antibody-drug conjugate for cancer therapy
Biography
Biography: Chuan-Lung Hsu
Abstract
Antibody drug conjugates (ADCs), a promising next generation antibody drug, combine tumor specifi city with highly potent cytotoxic payload for improve therapeutic effi cacy in cancer therapy. However, due to the manufacture issues and producing heterogeneous products of random conjugation of ADCs, here we report a highly effi cient glycogengineering technology by using a GnT-I (N-Acetyl glucosamine transferase I) and a GnTII (N-Acetyl glucosamine transferase II) as enzymes to conjugate a tri-mannosyl core antibody and produce an versatile ADC. Our results show that a homogenous tri-mannosyl Herceptin-2(GlcNAc-triazole-DBCO-(PEG)4-DM1)-2(GlcNAc-triazolDBCO-PEG4-Vc- PAB- (PEG)2-Duocarmycin) is generated with the conversion effi ciency over 90% and 50% recovery rate. Th e results indicate that the tri-mannosyl ADC has not only with highly potent cytotoxicity (IC50<1.2 nM) than Kadcyla, but also with better anti-tumor growth activity in BT-474 and N87 xenograft (TGI>90%).