Development of transplant immunosuppressive agents - considerations in the use of animal models
Department of Surgery, Division of Transplantation, UMass Memorial Medical Center
Animal Use Alternatives; Animals; Disease Models, Animal; Drug Development; Humans; Immunosuppressive Agents; Organ Transplantation; Rodentia; Species Specificity; Transplant Recipients
Animal Experimentation and Research | Bioethics and Medical Ethics | Immunology and Infectious Disease | Surgery | Surgical Procedures, Operative
INTRODUCTION: The development of all immunosuppressant agents to date has involved the experimental use of large and small animal models. Over the last half-century, immunosuppressive drugs have extended the lives of transplant patients worldwide. However, the use of animal models in the development of these drugs is not perfect, and this has brought to light a number of issues including idiosyncratic reactions that are found in animal models but not in humans. The 2006 highly publicized case of the 'elephant man' TGN 1412 drug trial highlights the importance of being cogent of the limitations of animal models.
Areas covered: This review covers the utility and limitations of the use of animal models for the development of immunosuppressant agents. This includes both large and small animal models, particularly rodent models in the transplant setting.
Expert opinion: The use of animal models represents a critical stage in the development of immunosuppressive drugs. Limitations include physiological differences to humans; this is especially true of immunologically naïve lab rodents with small memory cell populations. Toxic drug levels may differ widely between species. Animal models are also costly and raise ethical concerns. However, there is currently no way to recreate the complex environment of the human immune system purely in vitro.
Immunology, animal models, ethics, immunosuppressive drugs, large animal model, rodent model, tolerance, transplant
DOI of Published Version
Expert Opin Drug Discov. 2018 Nov;13(11):1041-1053. doi: 10.1080/17460441.2018.1535589. Epub 2018 Oct 17. Link to article on publisher's site
Expert opinion on drug discovery
Costello R, Kissenpfennig A, Martins PN, McDaid J. (2018). Development of transplant immunosuppressive agents - considerations in the use of animal models. Surgery Publications and Presentations. https://doi.org/10.1080/17460441.2018.1535589. Retrieved from https://escholarship.umassmed.edu/surgery_pp/178