Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the immune system attacking pancreatic islet cells. Nanoparticles coated with pMHC can induce antigen-specific regulatory T cells in vivo, thereby suppressing T1D disease without affecting general immunity. Creative BioMart provides solutions for the development of NPs carrying diabetes-related peptide-MHC-like complexes, advancing the development of specific therapeutic approaches against T1D and thus preventing and treating diabetes.

T1D-specific Therapy Based on pMHC-NPs

Current therapeutic approaches for autoimmune conditions are usually non-specific and may result in general immunosuppression. In contrast, regulatory T cells are expected to be therapeutic targets that do not compromise immunity, and several approaches are being taken to expand the regulatory population. However, studies have demonstrated that the use of disease-associated pMHC-NPs is particularly effective in attenuating autoimmune responses in autoimmune diseases.

Fig.1 pMHC-NPs act as artificial APCs to deliver antigenic signals to immune cells (Ni Q, et al., 2019)

In autoimmune T1D, the glucose-regulator insulin-producing β-cells in the pancreatic islets are selectively destroyed by the immune system, and while T1D can be successfully controlled with insulin replacement therapy, there has also been a search for ways to modify the underlying immunopathology of β-cell destruction, which requires the reinstallation of immune-tolerant β-cell antigens. Nanoparticles can act as artificial APCs by delivering antigenic signals to immune cells in the form of pMHC complexes, and treatment with pMHC-NPs has also been verified in mouse studies to significantly restore glucose normality and immune tolerance in diabetic mice.

Our Solutions

The use of specific antigens in combination with NPs for the treatment of T1D provides an innovative solution to improve the efficacy of immunosuppressive therapies. We offer our customers a range of services based on this strategy for the development of T1D-specific pMHC-NPs, including pMHC production, nanoparticle synthesis, pMHC coupling and quality control and characterization.

• pMHC production. Through bioengineering techniques to produce recombinant pMHC complexes, these autoantigen-specific pMHC complexes can expand autoantigen-specific regulatory CD4⁺ T cells and promote auto-reactive T cell differentiation, as well as induce and amplify regulatory B cells, further inhibiting T1D development by activating CD4⁺ T cells.
• Nanoparticle synthesis and coupling. To produce iron oxide nanoparticles, pMHC conjugation was accomplished by engineering to the free C-terminal Cys in the MHCα chain. pMHC conjugated NPs were purified by magnetic separation and concentrated by ultrafiltration and stored in PBS.
• Characterization of pMHC-NPs. To assess the pMHC concentration of pMHC-NP preparations by transmission electron microscopy, gel electrophoresis, SDS-PAGE and other analytical tools, to determine the pharmacokinetics, specificity, and bioavailability of nanomedicines by enzyme-linked immunosorbent assay, flow cytometry analysis, and statistical analysis.

Our Capabilities

• Engineering platform for pMHC complex production
• Ability to develop nanoparticles specifically coated with pMHC
• pMHC nanodrug-based assay platform

The pMHC-NPs can specifically trigger the formation and expansion of Treg cells associated with T1D. Creative BioMart offers the development of various pMHC-based nanomedicines and disease models, supporting the engineering of these compounds, as well as exploring potential mechanisms of action.

Please contact us to learn more about our services.

Reference

• Ni Q, et al. "Advances in Immunotherapy of Type I Diabetes." Advanced Drug Delivery Reviews (2019), 139,83-91.