From mice to men: the challenges of developing tolerance-inducing biological drugs for the clinic

  • Wan-Fai Ng
  • John D. Isaacs
Part of the Progress in Inflammation Research book series (PIR)


Before discussing the specific barriers to clinical therapeutic tolerance, it is useful to review the steps involved in biological drug development in general. The first is to identify an appropriate therapeutic target(s) based on current understanding of disease pathogenesis, which may be molecular or cellular in nature: an appropriately designed biologic that binds this target might reasonably be expected to influence the disease process. So-called “proof of concept” studies are then developed, typically in rodent models, to assess efficacy, safety, toxicity, immunogenicity, pharmacokinetics and metabolism of the newly developed biological drug. By their very nature, however, biological drugs that recognize animal targets generally will not recognize the equivalent human molecule. For instance, a monoclonal antibody (mAb) that binds murine CD3 will not recognize the human molecule due to inter-species differences in CD3 structure. Consequently, a different mAb must be developed for clinical studies, which will first be tested in in vitro and ex vivo studies using human cells or tissues, as well as in non-human primate models. Finally, the therapy will be evaluated in clinical trials.


Rheumatoid Arthritis Systemic Lupus Erythematosus Chronic Rejection Tolerance Induction Biological Drug 


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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Wan-Fai Ng
    • 1
  • John D. Isaacs
    • 1
  1. 1.Musculoskeletal Research Group, Institute of Cellular MedicineUniversity of NewcastleNewcastle upon TyneUK

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