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.
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