In vivo biotransformations of antibody–drug conjugates

Author:

Tumey L Nathan1,Rago Brian2,Han Xiaogang2

Affiliation:

1. Worldwide Medicinal Chemistry, Pfizer, Inc., Eastern Point Road, Groton CT 06340, USA

2. Pharmacokinetics, Dynamics & Metabolism, Pfizer, Inc., Eastern Point Road, Groton CT 06340, USA

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.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

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