TECHNOLOGY

LOCAL, ANTIGEN-SPECIFIC IMMUNOMODULATION

Creating DC regs to halt the cycle of autoimmunity

Type 1 Diabetes (T1D) is a disease of the immune system. In T1D, the immune system attacks and destroys the beta cells that produce the insulin required to regulate glucose levels. At the heart of this autoimmune attack are dendritic cells (DCs) — the “orchestra leaders” of the immune system that stimulate the autoimmune response causing T1D. Diavacs’ technology engineers the DCs that drive the autoimmune attack into “regulatory dendritic cells” (DC regs) that suppress the autoimmune attack.

Diavacs’ technology retrains DCs into DC regs by administering antisense oligodeoxynucleotides (AS-ODNs) against CD40, CD80 and CD86 – costimulatory proteins involved in the activation of T effector cells which attack beta cells. These DC regs adopt a restrained co-stimulatory ability and migrate to the pancreas and pancreatic lymph nodes (PLN) when injected into an abdominal region that is drained by those lymph nodes. In the PLN, DC regs take up beta cell antigens and adopt antigen specificity. The antigen-specific DC regs then regulate the immune response by 1) inducing T effector cell anergy and 2) increasing populations of regulatory cells that control the autoimmune response (specifically antigen-specific Foxp3+ T regulatory cells as well as B regulatory cells).

The Diavacs advantage

Given the significant unmet need of providing a better treatment alternative to patients with T1D, a number of products have been developed to modify the immune system to stop the autoimmune attack. Unfortunately, these approaches have been limited by inadequate effectiveness or systemic immunosuppression, which presents its own set of severe complications. Currently there are a number of early-stage approaches for creating more beta cells in T1D patients, but these new beta cells must still be protected from the autoimmune attack that drives the disease. DiaVacs potentially addresses the disadvantages of prior approaches by offering local antigen-specific immunosuppression, halting the pathogenic autoimmune response without compromising the body’s immune system, and complements emerging regenerative approaches by protecting newly created beta cells from autoimmune attack.