title: In vivo biotransformations of antibody-drug conjugates.
abstract: The selective delivery of potent pharmacologically active compounds to target tissue or cells by antibody-drug conjugates makes this immuno-conjugate a promising modality for the treatment of cancers. A thorough understanding of the structural integrity of the linker, the payload and the conjugation site during biological exposure is critical throughout the process of novel linker-payload design and optimization of PK profile. This understanding is a key aspect of the effort to maximize efficacy while minimizing toxicity in preclinical testing and to ensure the translation to the clinical setting. The complexity of this bioconjugate modality is a source of significant challenge for analytical interrogation and analysis in vivo. Therefore, we report herein a survey of various types of biotransformation events that have been elucidated in recent years.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer, Inc., Eastern Point Road, Groton CT 06340, USA.
authors.forename: L Nathan
authors.initials: LN
authors.lastname: Tumey
authors.affiliation: Pharmacokinetics, Dynamics & Metabolism, Pfizer, Inc., Eastern Point Road, Groton CT 06340, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rago
authors.affiliation: Pharmacokinetics, Dynamics & Metabolism, Pfizer, Inc., Eastern Point Road, Groton CT 06340, USA.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Han
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D001711:Biotransformation / Q000235:genetics*; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates