In vivo biotransformations of antibody-drug conjugates

• Published in: Bioanalysis Vol. 7; no. 13; pp. 1649 - 1664
• Main Authors: Tumey, L Nathan, Rago, Brian, Han, Xiaogang
• Format: Journal Article
• Language: English
• Published: England 01-01-2015
• Subjects: Antibodies, Monoclonal - immunology; Biotransformation - genetics; Humans; Immunoconjugates - immunology
• ISSN: 1757-6180; 1757-6199
• DOI: 10.4155/BIO.15.84

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.