H&E staining of colons from Zbtb20 WT and Zbtb20 cKO mice treated with DSS. Survival curves for WT and cKO mice following treatment with DSS in drinking water. Adoptive transfer of Zbtb20 expressing Tregs rescues mice from death and protects. Mice are also protected from excessive weight loss (not shown).
Invention Summary:
Inflammatory bowel diseases (IBD) are chronic idiopathic disorders causing inflammation of the gastrointestinal (GI) tract with a high prevalence rate. Specific and effective treatments for these diseases are limited. There is a clear need for therapy to treat inappropriate inflammatory responses in GI tissues, specifically by restoring normal immune regulation. A subtype of T cells - regulatory T cells (Tregs) - reside in the GI tissues have a key role in preventing unwanted immune responses, maintaining immune homeostasis and tissue-specific tolerance, and aid in balancing the gut microbiota.
Rutgers researcher, Derek Sant’Angelo, has discovered a subset of Tregs cells that is necessary for maintaining the barrier functions of the intestine and for controlling intestinal inflammatory disease. The CD4+ Tregs, were identified by their unique expression of the BTB-ZF transcription factor Zbtb20. Like other members of the BTB-ZF family, Zbtb20, is the “master regulator” of the unique effector functions of these T cells. Zbtb20-expressing Tregs accumulate in the intestine, specifically proliferate in response to epithelial damage and are essential for protecting the colon against inflammation. A key finding was that adoptive transfer of small numbers of Zbtb20-expressing Tregs was sufficient to protect the intestine from inflammation. Importantly, conventional T cells transduced with Zbtb20 acquire the functions and phenotype of the naturally occurring Tregs. These modified T cells, therefore, are expected to be effective as an adoptive T cell immunotherapy for treatment of IBD related diseases. Furthermore, monitoring the frequency of ZBTB20 expressing T cells in people may be predictive of susceptibility to disease.
Advantages:
- Novel Treg subset and its highly effective GI immune functions
- Key regulator of immune homeostasis in GI mucosa
- Tested in mice, can be evaluated in clinical settings
- Selective control of Treg function via gene transduction
Market Applications:
- Immunotherapy treatment method for inflammatory diseases
- Cell transfer therapy for treatment of IBD
- Method to assess risk of developing an inflammatory disease
Intellectual Property & Development Status: Patent pending. Available for licensing and/or research collaboration.
