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Chembiochem2025;26(2):e202400738.January 14, 2025Journal Article

Evaluation of Potency and Specificity of Cryptophycin-Loaded Antibody-Drug Conjugates.

Peter Bitsch1, Cedric Dessin2, Sebastian Bitsch1, Jona Voss2, Janine Becker1, Panna Sharma3, Neha Biyani3, Harry Kochat4, Norbert Sewald2, Harald Kolmar1,5
1Clemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
2Organic and Bioorganic Chemistry, Faculty of Chemistry, University of Bielefeld, Universitätsstraße 25, 33615, Bielefeld, Deutschland.
3Lantern Pharma Inc., 1920 McKinney Ave, 7th Floor, Dallas 75201, TX, USA.
4The University of Tennessee, Health Science Center, 208 S., Dudley Street, Memphis, 38163, TN, USA.
5Centre of Synthetic Biology, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
PubMed DOI

Abstract

An enhanced variant of the antimitotic toxin cryptophycin was conjugated to the anti-Her2 monoclonal antibody (mAb) Trastuzumab upon Michael addition. Either antibodies with freed hinge-region cysteines or THIOMAB formats with engineered cysteines in the mAbs light chain were added to a maleimide derivative of cryptophycin. These Antibody-Drug Conjugates (ADCs) showed retained binding to Her2 posi…

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