Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
作者： Jagath R Junutula , Helga Raab , Suzanna Clark , Sunil Bhakta , Douglas D Leipold
DOI: 10.1038/NBT.1480
关键词:
摘要: Antibody-drug conjugates enhance the antitumor effects of antibodies and reduce adverse systemic effects of potent cytotoxic drugs. However, conventional drug conjugation strategies yield heterogenous conjugates with relatively narrow therapeutic index (maximum tolerated dose/curative dose). Using leads from our previously described phage display–based method to predict suitable conjugation sites, we engineered cysteine substitutions at positions on light and heavy chains that provide reactive thiol groups and do not perturb …
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