WARF: P160186US02

Efficient In Vitro Assay for Antigen-Specific Tolerance


William Burlingham, Dario Vignali

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a T cell-bound cytokine assay for detecting antigen-specific immune suppression in transplant recipients or patients with autoimmune disease.
OVERVIEWThe ultimate goal of organ/tissue transplantation is drug-free acceptance, meaning the recipient’s body is able to tolerate the antigens derived from donor tissue (alloantigens). Unfortunately this scenario is rare, and immunotherapies with powerful side effects must be prescribed to prevent graft rejection.

Research has shown that those patients who are able to tolerate their grafts experience an active suppression of their immune response to specific antigens. The potential to induce such tolerance could help other transplant recipients or patients with autoimmune disorders.

To advance this research, UW–Madison faculty pioneered a method (called the trans vivo DTH bioassay) for measuring antigen-specific regulatory response in vertebrate animals. But there remains a need for a non-animal in vitro method.
THE INVENTIONBuilding on their work, UW–Madison researchers have now developed a T cell-bound cytokine (T-CBC) assay for detecting and quantifying regulatory T cells specific to self-antigens or donor alloantigens. The new method comprises (a) culturing the subject’s T cells for 24 hours in the presence of one or more target antigens and (b) analyzing the cultured T cells for expression of a marker (EBi3; TGFβ/LAP) indicative of antigen-specific immune suppression.
  • In vitro assay for measuring an antigen-specific regulatory response in patients
  • Identifying transplant recipients who are good candidates for cutting back or discontinuing immunosuppression
  • Applications in the cancer space, particularly in the area of DNA vaccines and immunotherapy
  • Performed on the same 24-hour time scale as the DTH bioassay but requires far fewer cells
  • Avoids the need for vertebrate animals
  • Amenable to automation and miniaturization
  • Supports a variety of applications, including clinical laboratory use
STAGE OF DEVELOPMENTThe researchers have demonstrated the utility of the assay in mouse cells. They have a conducted a preliminary experiment with human cells using human colV-specific regulation of TGFβ-LAP. Surface EBi3 experiments with human cells are in progress. Future direction will focus on miniaturization.
For More Information About the Inventors
Contact Information
For current licensing status, please contact Rafael Diaz at or 608-960-9847.
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