Dysregulated immune cells targeting and destroying pancreatic islets and neurons is a hallmark of Type 1 diabetes and many central nervous system (CNS) diseases, respectively. Over 2.2 million people in the US are affected by Type 1 diabetes while about 23.5 million people in the US are affected by autoimmune diseases, such as multiple sclerosis which affects the CNS.
Regulatory T cell (Treg) therapy can be used to treat such diseases. However, polyclonal Tregs are nonspecific, reducing their efficacy and unwanted side effects outside the diseased tissue. Specifically targeting Tregs to the organ of interest could be key to curing such diseases rather than merely treating symptoms. Dipeptidyl Peptidase Like 6 (DPP6), is known to be expressed in islet and CNS cells. UCSF scientists have engineered regulatory T cells (Tregs) that express anti-DPP6 chimeric antigen receptors (CAR). This new property enables Tregs to traffic and accumulates in the pancreatic islets and CNS to subdue unwanted autoimmune reactions in these tissue with great precision. Preclinical findings demonstrate the feasibility of the new approach:
1. Several versions of anti-DPP6 CAR are expressed on the surface of primary human CD4+ T cells and Tregs.
2. Human T cells expressing anti-DPP6 CARs are activated by isolated human islets in vitro.
3. Anti-DPP6 CAR human CD4+ T cells and Tregs traffic to the CNS and transplanted human pancreatic islets in immunodeficient mice.
1. Anti-DPP6 CARs enable efficient targeting of T cells to pancreatic islets and CNS.
2. When expressed in Tregs, anti-DPP6 CARs can trigger immunosuppressive function of the Tregs locally to dampen inflammation - the root cause of the disease.
3. Compared with polyclonal Treg cell-based therapy, anti-DPP6 CAR-expressing Tregs are likely to be more potent and specific.
4. Lower risk of treatment resistance and off-target immunosuppression compared to polyclonal Treg therapy.
Name: Kathleen Wilson-Edell