title: Current Status: Site-Specific Antibody Drug Conjugates.
abstract: Antibody drug conjugates (ADCs), a promising class of cancer biopharmaceuticals, combine the specificity of therapeutic antibodies with the pharmacological potency of chemical, cytotoxic drugs. Ever since the first ADCs on the market, a plethora of novel ADC technologies has emerged, covering as diverse aspects as antibody engineering, chemical linker optimization and novel conjugation strategies, together aiming at constantly widening the therapeutic window for ADCs. This review primarily focuses on novel chemical and biotechnological strategies for the site-directed attachment of drugs that are currently validated for 2nd generation ADCs to promote conjugate homogeneity and overall stability.
authors.affiliation: Chemical Biology and Department of Chemistry, Leibniz-Institut für Molekulare Pharmakologie and Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schumacher
authors.affiliation: Chemical Biology and Department of Chemistry, Leibniz-Institut für Molekulare Pharmakologie and Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Christian P R
authors.initials: CP
authors.lastname: Hackenberger
authors.affiliation: Department of Biology II, Ludwig-Maximilians-Universität München and Center for Integrated Protein Science Munich, Planegg-Martinsried, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Leonhardt
authors.affiliation: Department of Biology II, Ludwig-Maximilians-Universität München and Center for Integrated Protein Science Munich, Planegg-Martinsried, Germany. helma@biologie.uni-muenchen.de.
authors.forename: Jonas
authors.identifier: 0000-0001-6158-452X
authors.initials: J
authors.lastname: Helma
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001709:Biotechnology / Q000379:methods / Q000639:trends; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000639:trends
chemical_list: D000596:Amino Acids; D004220:Disulfides; D018796:Immunoconjugates
keywords: Antibody drug conjugates (ADCs); Sortase A; THIOMAB; Tub-tag; drug-antibody ratio (DAR); formylglycine generating enzyme (FGE); microbial transglutaminase (MTG); monomethyl auristatin E/F (MMAE/MMAF); site-specific conjugation; therapeutic window; tubulin tyrosine ligase (TTL); unnatural amino acids (UAA)