Generation of Stable iTregs as Therapeutics against Autoimmune Diseases (Type I Diabetes)

Description:

Project ID: D2010-30

 

Invention novelty:

New methods for induction and expansion of stable iTregs without addition of exogenous TGF-β

 

Value Proposition:

The “anti-self” immune response in human body leads to development of autoimmune diseases. For example, Diabetes mellitus type 1 (formerly known as juvenile diabetes) results from autoimmune destruction of insulin-producing beta cells of the pancreas. The natural Treg (nTreg) cells and inducible Treg (iTreg) cells regulate the immune system to suppress autoimmune diseases and TGF-β (transforming growth factor- β) induced conversion to iTregs has been explored in the past for the application as future therapy for autoimmune diseases. However this method proved to be unreliable and produces unstable iTregs, easily losing both Foxp3 expression and suppressor function upon environmental change and after repeated re-stimulation.

The disclosed technology embodies three new methods for induction of stable iTregs without addition of exogenous TGF-β. These methods may be used to produce ex vivo large quantities of iTregs for an in vivo therapy of patients with autoimmune diseases and for prevention of allograft rejection. All these unique methods share a common two-phase culture condition with an induction phase and an expansion phase.  The other advantages include:

·       Downmodulates immune response for certain autoimmune disorders, and host vs. graft response due to transplant.

·       Reduces T-cell numbers in vivo or in vitro

·       In vivo results show that method enriches Treg cells, arrests T-cell response to antigen, and prevents cytokine storm.

·       Identifies test compounds useful to enrich Treg cells.

 

Invention Description:

Researchers in the department of Medical Microbiology and Immunology in the College of Medicine at the University of Toledo have established three new methods for induction of stable iTregs. All the three methods consist an induction phase, comprising contacting a naive CD4 T cell with a stimulatory signal and an appropriate amount of a combination of factors, followed by an expansion phase, with a fresh culture medium containing an appropriate amount of protein that regulates the activities of white blood cells. Researchers have demonstrated that the generated regulatory T cell expresses forkhead 3 (Foxp3) transcription factor, a GITR marker, a CTLA4 marker, a CD25 marker, and suppresses 80% proliferation of an effector T cell in an in vitro suppressor assay at the 1:1 ratio. These methods may be used to produce a therapy for patients with autoimmune diseases and reduce or eliminate allograft rejection.

 

Applications:

·       Preventing and treating autoimmune diseases including Type 1 diabetes.

·       Ameliorating inflammation for certain conditions including stroke, vascular disease, cancer, sepsis, fever, injury, burn, toxin exposure, infection, radiation, poisoning, and allergic reaction.

·       Reducing or eliminating transplant rejection including graft, partial organ transplant and full organ transplant.

·       Reducing the risk of adhesions and/or neurological, vascular or muscle tissue impairment after a surgical procedure in a surgical patient.

 

IP Status: United States Patent 9,018,006

Publications:

1.     "Default" generation of neonatal regulatory T cells [Link]

2.     A Dynamic Dual Role of IL-2 Signaling in the two-step differentiation process of adaptive regulatory T-cells [Link]

 

Patent Information:
For Information, Contact:
Stephen Snider
AVP Tech Transfer
The University of Toledo
419 530 6225
Stephen.Snider@utoledo.edu
Inventors:
Stanislaw Stepkowski
Whenhao Chen
Yoshihiro Miyahara
Keywords:
Autoimmune
iTregs
Type I diabetes