Cited by 121Animal testing and alternativesImmunotoxicology and immune responsesMonoclonal and Polyclonal Antibodies Research

Preclinical safety testing of monoclonal antibodies: the significance of species relevance

Chapman, Kathryn, Pullen, Nick, Graham, Mark, Ragan, Ian·2007·Nature Reviews Drug Discovery

Abstract

Selecting a pharmacologically relevant animal species for testing the safety and toxicity of novel monoclonal antibody (mAb) therapies to support clinical testing can be challenging. Frequently, the species of choice is the primate. With the increased number of mAbs in the pharmaceutical pipeline, this has significant implications for primate use, and so raises several important scientific, ethical and economic issues. Here, following a recent international workshop held to debate this topic, we discuss issues in the preclinical testing of mAbs, with a particular focus on species relevance and primate use, and provide suggestions for how these issues might be addressed.

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Crossref · 10.1038/nrd2242

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18 of 18 references verified0 citation errors · 0 not checkable

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  • The specific choice for FIH dose depends on several factors: species cross-reactivity, relevance of animal models, steepness of dose response, PK/PD relationship, nature of toxicity, and precedence of molecules in similar pathways.

    “The specific choice for FIH dose depends on several factors: species cross‐reactivity, relevance of animal models, steepness of dose response, PK/PD relationship, nature of toxicity such as predictability, reversibility, tolerability, manageability, and the precedence of molecules in similar pathways.70”

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Authors
Chapman, K., Pullen, N., Graham, M., & Ragan, I.
Affiliations
  • National Centre for the Replacement Refinement and Reduction of Animals in Research (GB)
  • Pfizer (United Kingdom) (GB)
  • AstraZeneca (United Kingdom) (GB)
  • Eli Lilly (United Kingdom) (GB)
Corresponding author
Chapman, Kathryn
Venue
Nature Reviews Drug Discovery
Published
2007-02
Volume
6
Issue
2
Pages
120-126
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
OpenAlex
W2064876070
Cited by
121
References
18
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 5 · 2013: 11 · 2012: 16
FWCI
2.76
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Centre for the Replacement, Refinement and Reduction of Animals in Research
  • National Centre for the Replacement Refinement and Reduction of Animals in Research
Topics
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
monoclonal antibodies, preclinical safety, non-human primates, animal ethics, translational animal model
MeSH terms
Animals, Antibodies, Monoclonal, Drug Evaluation, Preclinical, Primates, Toxicity Tests, Animals, Genetically Modified

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