Push/pull immunomodulation liposomes for antigen-specific treg therapy in anti-gbm disease

Overview

This research program develops a targeted immunomodulation therapy for anti-glomerular basement membrane (anti-GBM) disease, a rare autoimmune condition that causes rapid kidney and lung damage. The approach, called Push/Pull Immunomodulation (PPI), uses liposomes—tiny lipid-based delivery vesicles—to co-package three components: a disease-relevant antigen, an immune agonist ("push"), and an immunosuppressive drug ("pull"). Once administered, these liposomes are taken up by local antigen-presenting cells and steer them toward a tolerogenic phenotype. These tolerogenic dendritic cells then promote the differentiation of antigen-specific regulatory T cells (Tregs), which suppress the autoimmune attack driving anti-GBM disease. Because the platform is antigen-flexible, it can be adapted to other rare or orphaned autoimmune diseases where the target antigen is known.

Technical specifications

Core technology:

• Liposomal delivery system co-encapsulating antigen, immune agonist, and immunosuppressive drug
• Mechanism reprograms dendritic cells toward tolerogenic phenotypes expressing PD-L1 and IL-10
• Induces antigen-specific Tregs that suppress targeted autoimmune responses without broad immunosuppression
• Formulation optimized through high-throughput screening of over 40,000 agonist/inhibitor combinations, yielding 10 candidate combinations showing greater than 10-fold increase in IL-10 secretion

Key advantages:

• Antigen-specific targeting reduces off-target immune suppression compared to conventional immunosuppressive therapies
• Modular design allows swapping antigens to address different autoimmune diseases
• Built on a previously validated platform demonstrated in mouse models of multiple sclerosis
• Potential to address rare and orphaned autoimmune conditions with limited treatment options

Technology readiness level

The underlying PPI-liposome platform has been validated in published mouse model studies of multiple sclerosis, demonstrating generation of tolerogenic dendritic cells and antigen-specific Tregs that suppressed disease. The current program focuses on adapting the platform to anti-GBM disease. Initial in vitro optimization of PPI combinations and validation of liposomal loading with anti-GBM antigens is planned over the next 8 to 12 months, followed by in vivo testing in anti-GBM disease mouse models to confirm suppression of pathogenic autoantibodies and disease progression. The technology is currently at an early-stage research and preclinical development phase, with guidance sought on the most critical antigens for anti-GBM and related rare autoimmune diseases.