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Regulatory T Cells with Chimeric Antigen Receptors to Improve Treatment of Hemophilia A

Technology #16912

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Roland Wilfried Herzog
Moanaro Biswas
Todd Michael Brusko
Managed By
Anita Rao
Assistant Director 352-392-8929

Tolerizes immune system from developing neutralizing antibodies to factor VIII

These FVIII-specific regulatory T cells (Tregs) suppress immune responses to clotting factor VIII used in treating Hemophilia A. Hemophilia A results from a deficiency in clotting factor VIII (FVIII), and its symptoms include abnormal bleeding and poor blood clotting. Hemophilia A affects about one in every 5,000 births and is four times as common as hemophilia B. Currently, treatment of hemophilia A consists of intravenous delivery of clotting factor FVIII. However, the immune system recognizes this as foreign and the patient develops inhibitors to the Factor VIII that prevent its function. While Immune tolerance induction (ITI) protocols exist for eradicating inhibitory antibodies, the process to induce tolerance takes more than a year, is expensive and fails about 30 percent of the time. Adoptive immunotherapy with T regulatory cells of polyclonal specificity is used in the clinic for graft versus host disease, in organ transplantation, and other autoimmune indications; however no antigen specific Treg based tolerance therapies are available.

Researchers at the University of Florida have developed a chimeric antigen receptor with antigen specificity that will suppress the development of immune responses directed at FVIII used therapeutically in hemophilia A patients. The chimeric antigen receptors can successfully combine this specificity with Treg cell function to suppress both T and B cells involved in inhibitor formation.


Factor FVIII specific CAR Tregs to suppress inhibitory antibody formation in response to FVIII replacement therapy for hemophilia A


  • Reduces severe side effects and risk of long-term damage to the immune system, allowing the treatment of hemophilia A to be safer and more efficient
  • Utilizes fewer Tregs to induce tolerance to FVIII replacement therapy than existing Treg-based therapies
  • Suppresses both T and B cells involved in inhibitor formation
  • CAR-Tregs can effectively generate a large pool of antigen specific cells with no requirement for MHC restriction


This T-cell therapy consists of CAR-engineered T regulatory cells that show antigen specific binding, activation and proliferation independent of MHC recognition. The CAR vector construct consists of a single chain antibody variable region (scFv) derived from an antibody developed in patients as well as signaling domains that activate T cells in response to FVIII. This antigen-specific activation leads to Treg cell activation to constrain host FVIII-reactive T cells and antibody-producing B cells in a controlled manner. This technology offers antigen-specific tolerance in hemophilia and can help to maximize potency, stability, persistence and specificity of engineered T cells and help patients who have failed immune tolerance induction.

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