Design, Synthesis, and invitro Evaluation of Multivalent Drug Linkers for High-Drug-Load Antibody-Drug Conjugates

• Published in: ChemMedChem Vol. 13; no. 8; pp. 790 - 794
• Main Authors: Chen, Bo, Gianolio, Diego A., Stefano, James E., Manning, Charlene M., Gregory, Richard C., Busch, Michelle M., Brondyk, William H., Miller, Robert J., Dhal, Pradeep K.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 23.04.2018
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; trastuzumab; polyethylene glycol; EFFICACY; antibody-drug conjugates; CANCER; CHALLENGES; multivalent drug linkers

A series of novel multivalent drug linkers (MDLs) containing cytotoxic agents were synthesized and conjugated to antibodies to yield highly potent antibody-drug conjugates (ADCs) with drug/antibody ratios (DARs) higher than those typically reported in the literature (10 vs. approximate to 4). These...