Antibody Drug Conjugates: Nonclinical Safety Considerations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-09

AUTHORS

Mary Jane Masson Hinrichs, Rakesh Dixit

ABSTRACT

Antibody drug conjugates (ADCs) are biopharmaceutical molecules consisting of a cytotoxic small molecule covalently linked to a targeted protein carrier via a stable cleavable or noncleavable linker. The process of conjugation yields a highly complex molecule with biochemical properties that are distinct from those of the unconjugated components. The impact of these biochemical differences on the safety and pharmacokinetic (PK) profile of the conjugate must be considered when determining the types of nonclinical safety studies required to support clinical development of ADCs. The hybrid nature of ADCs highlights the need for a science-based approach to safety assessment that incorporates relevant aspects of small and large molecule testing paradigms. This thinking is reflected in current regulatory guidelines, where sections pertaining to conjugates allow for a flexible approach to nonclinical safety testing. The aim of this article is to review regulatory expectations regarding early assessment of nonclinical safety considerations and discuss how recent advances in our understanding of ADC-mediated toxicity can be used to guide the types of nonclinical safety studies needed to support ADC clinical development. The review will also explore nonclinical testing strategies that can be used to streamline ADC development by assessing the safety and efficacy of next generation ADC constructs using a rodent screen approach. More... »

PAGES

1055-1064

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1208/s12248-015-9790-0

    DOI

    http://dx.doi.org/10.1208/s12248-015-9790-0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1038979073

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26024656


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