Selectively culturing and programming regulatory T-cells (Tregs) to help restore tolerance in autoimmune disease
Autoimmune diseases are a diverse family of pathologies that lead to the morbidity and mortality of millions of people worldwide. Indeed, some estimates place the prevalence of this disease family as high as 20% of the American population, equating to over 50 million current cases, many of which are hereditary and have profound impacts on children and adults alike. Recent research has helped elucidate the role of Treg imbalance relative to effector t-cells. This imbalance has been linked to such autoimmune diseases as type I diabetes, Crohn’s disease, multiple sclerosis, ulcerative colitis, and rheumatoid arthritis and has profound implications for alloimmune disorders such as graft-versus- host-disease and graft rejection.
Dr. Scott FurlanDr. Leslie Kean
The work conducted by Drs. Kean and Furlan aims to attenuate autoimmune/alloimmune disease progression by restoring balance between the populations of effector t-cells and Tregs. The team has made significant advances in culturing and purifying Tregs at levels suitable for therapeutic application. Further work by Kean’s group has shown that purified Treg cultures can then be conditioned to exhibit improved allo-immunity suppression by pulsing with sirolimus. These results show promising applicability in treating graft vs. host disease and improving the outcome of whole organ transplants.
Amongst the more recent advancements made by Kean’s group is the stabilization of Tregs’ therapeutic phenotype during clinical application so as to reduce the loss of FoxP3 expression and maintain a more suppressive T cell pool. Application of rapamycin during Treg therapies has shown not only significant retention of CD25 and FoxP3 expression, but introduces over a twofold improvement to Treg half-life as well.
Scientific progress led by Drs. Kean and Furlan has helped develop one of the most advanced in vivo autoimmunity models in the world, and indeed one of the most analogous to human pathology. The robust research infrastructure and knowledge base maintained by this group could provide great partnering benefits such as a high fidelity pre-clinical test platform for autoimmune diseases, and the development of homogenized immuno-privileged Treg cell lines.
Stage of Development
- Pre-clinical in vitro
- Pre-clinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Consultation agreement
- Licensing agreement
- Clinical trial
- Singh K, Stempora L, Harvey RD, Kirk AD, Larsen CP, Blazar BR and Kean LS. 2014. Superiority of Rapamycin over Tacrolimus in Preserving Non-human Primate Treg Half- life and Phenotype After Adoptive Transfer. Am J. Transplant. 2014 Dec;14(12):2691-703.
- Singh K, Kozyr N, Stempora L, Kirk AD, Larsen CP, Blazar BR and Kean LS. 2012. Regulatory T cells Exhibit Decreased Proliferation but Enhanced Suppression After Pulsing with Sirolimus. Am. J. of Transplant. February 2, 2012 [Epub ahead of print].
- Kean LS, Sen S, Onabajo O, Singh K, Robertson J, Stempora L, Bonafacino AC, Metzger ME, Promislow DEL, Mattapallil JJ, and Donahue, RE. 2011. Significant Mobilization of Both Conventional and Regulatory T cells with AMD3100. Blood. 15;118(25):6580-90.
- Anderson A, Martens C, Hendrix R, Stempora K, Miller W, Hamby K, Russell N, Strobert E, Blazar BR, Pearson TC, Larsen CP and Kean LS. 2008. Expanded Non- human Primate Tregs Exhibit A Unique Gene Expression Signature and Potently Downregulate Allo-immune Responses. Am J. Transplant. Nov 8(11)2252-2264.
To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:
Dr. Elizabeth Aylward
Director, Office of Science-Industry Partnerships