Site-Specific Dual Antibody Conjugation via Engineered Cysteine and Selenocysteine Residues

Bioconjug Chem. 2015 Nov 18;26(11):2243-8. doi: 10.1021/acs.bioconjchem.5b00244. Epub 2015 Jul 24.

Abstract

Site-specific conjugation technologies enable the production of homogeneous antibody-drug conjugates (ADCs) with improved therapeutic indices compared to conventional ADCs. However, current site-specific conjugation methods can only attach one type of drug to a single antibody. Given the emergence of acquired resistance to current ADCs, arming single antibodies with different drugs may provide an attractive option in the development of next-generation ADCs. Here, we describe a site-specific dual conjugation strategy as a platform for dual warhead ADCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cysteine / chemistry*
  • Humans
  • Immunoconjugates / chemistry*
  • Selenocysteine / chemistry*
  • Trastuzumab / chemistry*

Substances

  • Immunoconjugates
  • Selenocysteine
  • Cysteine
  • Trastuzumab