Tu109 - SQZ® TAC Cell Therapy Platform Induces Antigen Specific T-regs and Prevents Onset of Type 1 Diabetes in Adoptive Transfer Models

Antigen specific tolerance is a preferred therapeutic mode of promoting durable disease remission in autoimmune diseases with well-defined antigens and could overcome the problems associated with broad immunosuppression. The Cell Squeeze® technology utilizes microfluidic mechanical deformation to engineer cell function. To induce tolerance, red blood cells (RBCs) are engineered to deliver target antigens to generate tolerizing antigen carriers (TACs). The Cell Squeeze technology allows the SQZ®TACs to resemble senescent RBCs, enabling them to be cleared by eryptosis, the physiological mechanism of RBC clearance. Herein, we demonstrate SQZ TACs biodistribute to phagocytic cells in the spleen and liver where antigens are processed and presented to antigen specific T-cells in a tolerogenic manner. SQZ TAC treatment in several accelerated murine models of T1D led to significant delay or prevention of hyperglycemia. In both CD4+ (BDC2.5) and CD8+ (NY8.3) NOD adoptive transfer T1D models, co-delivery of TAC loaded with T1D autoantigens provided protection from early disease onset characterized by increased T-cell apoptosis, tissue specific T-reg induction and decreased effector T-cell pancreatic infiltration. In addition, administration of a CD4+ directed TACs with the peptide p31 protected T1D onset in NOD mice co-transferred with both BDC2.5 and NY8.3 T cells, thereby demonstrating TAC induced bystander suppression. Recent preclinical efforts have expanded to include development of a TAC-deamidated gliadin formulation to ameliorate gluten sensitivity in patients suffering with Celiac Disease.