Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1...

Area of Science:

• Immunology
• Biotechnology
• Cell Therapy

Background:

• Autoimmune diseases require therapies that selectively suppress autoreactive T cells without causing systemic immunosuppression.
• Current treatment strategies often lack specificity and efficacy, necessitating novel approaches.

Purpose of the Study:

• To develop and evaluate tolerizing antigen carriers (TACs) using microfluidic Cell Squeeze technology for antigen-specific immune tolerance.
• To assess the therapeutic potential of TACs in preclinical models of autoimmune diseases, specifically type 1 diabetes (T1D).

Main Methods:

• Engineering red blood cells (RBCs) to encapsulate antigens using Cell Squeeze technology to create TACs.
• Evaluating TAC efficacy in mouse models of T1D, including immunization and adoptive transfer studies.
• Investigating the mechanistic basis of TAC-induced tolerance, focusing on T cell trafficking, deletion, and regulatory T cell (Treg) expansion.

Main Results:

• TAC treatment successfully induced antigen-specific T cell tolerance to both exogenous and autoantigens in mouse models.
• TACs prevented hyperglycemia in accelerated T1D models by suppressing pathogenic T cell effector functions, particularly in the pancreas.
• Mechanistic studies revealed impaired diabetogenic T cell trafficking, deletion of autoreactive CD8 T cells, and expansion of Tregs with bystander suppression.

Conclusions:

• TACs represent a novel cell-based therapeutic approach for inducing antigen-specific immune tolerance.
• This technology holds promise for treating T cell-mediated autoimmune diseases, including those affecting CD4 and CD8 T cells.
• TACs leverage natural RBC clearance pathways for tolerogenic antigen presentation, offering a unique therapeutic strategy.