IBD is mediated by bowel epithelium cells and by immune cells such as infiltrating T lymphocytes and macrophages known to be key components of the disease progression via the secretion of inflammatory cytokines like TNFα. Classical IBD murine models do not offer the possibility to assess human-specific drugs targeting human-specific immune cells or human cytokines such as hTNFα. However, reconstitution of a fully functional human immune system in the NOG mouse (huNOG) with both lymphoid and myeloid lineages reconstitution is ideal for the profiling of human specific drug targets such as human anti-hTNFα.

Acute and/or chronic IBD can be induced in huNOG mice by addition of Dextran Sulfate Sodium (DSS) in the drinking water or TNBS in the colon. A clinical scale has been developed to score the severity of the IBD disease progression or regression. Body weight, stool consistency, rectal bleeding and mortality have been scored and were presented.

TransCure bioServices also showed that the reconstituted human immune system plays a key role in the severity and the prolongation of the disease itself. In addition, in response to DSS, human leukocytes are able to infiltrate the murine colon and participate to the inflammation process by secreting human inflammatory cytokines like hTNFα. We showed the level of efficacy of cyclosporin-A and of anti-hTNFα monoclonal antibody in the huNOG IBD models (acute and chronic protocol designs). We have collected more than >400 huNOG IBD mouse data with small molecules or biologics and positive/negative control arms.

Presenters:

Dr. Patrick Nef is Chief Executive Officer and Founder at TransCure bioServices SAS. He holds a PhD in Molecular Neurobiology from the University of Geneva, Switzerland. He has more than 30 years of experience as Assistant Professor at the Univ. of Geneva, Vice-Director at F. Hoffmann-La Roche, ltd, Basel and CSO, CBO and CEO for several biotechnology driven companies. In 2012, he founded TransCure bioServices SAS. Patrick Nef has published more than 50 peer-reviewed publications and patents in the field of sensory olfaction, learning and memory, and calcium sensors.

Dr. Patrick Nef
 
Dr. Sebastien Tabruyn is Chief Scientific Officer at TransCure bioServices SAS. He holds a PhD in Molecular Biology from the University of Liege (Belgium). After 10 years of experience as project leader in renowned international academic research institutes including UCSF (California, USA), the Centre for Cancer Biology (Adelaide, Australia) and the University of Maastricht (Netherlands), he joined TransCure bioServices in 2013 as Head of Molecular Biology and Oncology. Sebastien Tabruyn has published 30 peer-reviewed publications in the fields of oncology, angiogenesis and inflammation.
Dr. Sebastien Tabruyn

Key Learning Points:

  • How humanized immune system mice can be used to model human IBD

  • Different methods to induce IBD in humanized mice

  • How IBD can be scored in huNOG mice

  • How engrafted human leukocytes infiltrate the mouse colon and participate in inflammation

  • How drug candidates can be profiled in the humanized mouse model of IBD

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© 2018 Taconic Biosciences, Inc. All rights reserved.

© 2018 Taconic Biosciences, Inc. All rights reserved.