Citation

While there has been extensive development of soluble epitope-specific peptides to induce immune tolerance for the treatment of autoimmune diseases, the clinical efficacy of soluble peptides-based immunotherapy was still uncertain. Recent strategies to develop antigen carriers coupled with peptides have shown promise results in preclinical animal models. Here we developed functional amphiphilic hyperbranched polymers with different grafting degrees of hydrophobic chains as antigen MOG peptide carriers and evaluated their ability to induce immune tolerance. We hypothesized that the infusion of lipophilic chain with cellular membrane can enhance the peptide uptake. We show that these polymers could efficiently deliver antigen peptide, and the uptake amount by bone marrow DCs (BMDCs) was correlated with the hydrophobicity of polymers. We observe that these polymers have higher ability to activate BMDCs and higher efficacy to induce antigen-specific T cell apoptosis than soluble peptide, irrespective of hydrophobicity. We show that intravenous injection of polymers conjugated myelin antigen oligodendrocyte glycoprotein (MOG) peptide, but not soluble peptide, markedly treat the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in mice. Together, these results demonstrate the potential for using amphiphilic hyperbranched polymers as antigen carriers to deliver peptides for pathogenic auto-reactive T cells deletion/tolerance strategies to treat autoimmune disorders.