Targeting Pathogenic T Cell Subsets for Elimination or Reprograming Through the Use of Engineered Chimeric Receptors (Ecr)Technology #ua14-187
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Autoimmune diseases are caused by cellular responses from immune system attacking self antigens. Such disorders include Type 1 diabetes, multiple sclerosis, rheumatoid arthritis, Systemic lupus erythematosus (SLE), certain peripheral neuropathies, Hashimoto’s Thyroiditis, Chron’s disease, and allergic contact dermatitis (ACD), among others. In recent years, considerable research has been put into modifying T lymphocytes to reprogram them to kill tumor cells. This research has resulted in technologies such as Chimeric Antigen Receptors (CARs) and the introduction of ectopic T Cell Receptors (TCRs) into T cells and use these cells to treat cancer patients (usually through the process of adoptive cell transfer of T cells – i.e. removing the patient’s own T cells and altering their immunologic functionality before reintroducing them into the patient’s immune system). Inventors at U of Arizona and Joslin Diabetes center have converted this technology to kill T cells with autoimmune potentials.
The present invention is a novel, human engineered, chimeric cell surface protein complex that is expressed on the surface of a patient’s own T cells, called an Engineered Chimeric Receptor (ECR). This ECR transforms the functionality of some of the patient’s own T cells, allowing them to specifically target the subset of T cells in each individual patient’s immune system that are recognizing self-antigens while sparing the patient’s healthy and normally functioning T cells. This minimizes or eliminates negative side effects on immune function.
? Selectively target and then eliminate specific T cells that are involved in autoimmune responses.
? Selectively target regulatory T cells that are inhibiting anti-tumor responses.
? Selectively target a subset of T cells that are attacking self tissues.
? The chimeric protein is very different from the usual chimeric receptor design.
This technology has been tested in vivo in murine diabetes model and the T cells that express the ECR can prevent type I diabetes in mice.
Lead Inventor: Michael Kuhns, PhD and Thomas Serwold, PhD
Licensing Manager: Lisa Lin, PhD