Advancing IBD Research
A closer look at the T-cell transfer model
Why T-Cell Transfer is the Gold Standard
Pre-clinical drug development requires relevant and dependable models to benchmark the efficacy of therapeutic agents. Adoptive T cell transfer-mediated colitis is regarded by many as the gold standard model for testing new treatments for Inflammatory Bowel Disease. Epistem has more than 15 years experience in running this model as a service and it is a core offering in our Inflammation portfolio. In this review, we will highlight its key attributes and how it can be employed to meet the needs of your research programme.
- Naïve T cells from immunocompetent donors drive colitis in congenic/syngenic immunocompromised recipients.
- Colitis development is dependent on T cell migration to the bowel and a T cell-mediated adaptive immune reponse to microbiome-derived antigens.
- The Th1/Th17 immunophenotype is similar to that observd in Crohn’s disease.
- Histopathological features of disease include: epithelial hyperplasia, mixed inflammatory cell infiltration into the mucosa and sub-mucosa, goblet cell depletion, crypt abscess formation, erosion and ulceration.
- Regional variation in disease severity within the large bowel.
- Disease in the model is responsive to a range of newer classes of therapeutic agents recently licenced for treatment of IBD, such as anti-cytokine antibodies, tyrosine kinase inhibitors and sphingosine-1 phosphate receptor modulators.
- Regional variation in therapeutic efficacy within the large bowel.
- Customisable model with options for prophylactic and therapeutic administration regimens, over a 4 to 7 week period.
A range of donor/recipient pairings are available.
Adoptive T cell transfer-mediated colitis is a validated and dependable model for inflammatory bowel disease, backed by a dedicated scientific team and portfolio of model performance data. In addition, Epistem can support this model with a range of analytical platforms and assays to offer you a service that is tailored to the needs of your research programme.
- In-life disease monitoring, with scheduled and on-demand access to the project team.
- Evaluation of T cell engraftment by flow cytometry.
- Additional in-life disease monitoring using intestinal permeability assays and ELISA-based assays of faecal biomarkers.
- Evaluation of gross pathology at study end including large bowel weight and length and spleen weight.
- Isolation and characterisation of leukocyte populations from spleen, lymph nodes and intestine using flow cytometry.
- Full histology service including blinded evaluation of large bowel histopathology with option for immunohistochemistry using a wide range of validated antibodies.
- Luminex-based multiplex cytokine assays using tissue lysate/plasma/serum samples.
- Collection of additional samples according to Sponsor’s sepcification, including provision of samples for pharmacokinetic analysis, at defined times post-administration of test therapeutics.
- Full range of gene expression profiling services available via our pharmacogenomic lab.