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pMHC-NPs Development for Liver Autoimmune Pathologies

pMHC-based nanodrugs can display tissue-specific autoantigenic epitopes that attenuate specific autoimmune conditions by reprogramming antigen-experienced CD4+ T cells into disease-suppressing T regulatory type 1 (TR1) cells. Liver autoimmune disease is an organ-specific autoimmune disease in which the autoimmune response is focused on non-organ-specific antigens enriched in the liver. pMHC-NPs are able to exhibit antigens associated with but commonly expressed in liver autoimmune diseases, attenuating various liver autoimmune diseases in a non-disease-specific manner without suppressing local or systemic immunity to infectious agents or cancer.

Creative BioMart provides pMHC-based nanomedicine development services that display various epitopes associated with liver autoimmune diseases, trigger the formation and expansion of specific TR1 cells, and are widely used to treat various liver autoimmune diseases.

pMHC-NP Therapy for Liver Autoimmune Pathologies

Autoimmune disorders in the liver have multiple disease manifestations, including primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Although PBC, PSC and AIH are considered distinct diseases, they all result from autoimmune reactions that recognize autoantigens that are commonly expressed in the liver.

In this context, pMHC-based nanomedicines shown to be derived from antigenic epitopes associated with a disease may be able to trigger the formation and expansion of site-specific TR1 cells, thereby attenuating the corresponding liver autoimmune disease. In addition to attenuating the corresponding hepatic autoimmune disease, it may also attenuate unrelated conditions. The specific mechanism is the formation and expansion of various pMHC-NPs by triggering the formation of homologous TR1-like CD4+ T cells, inhibition of the pro-inflammatory and antigen-presenting capacity of local and proximal APCs, and formation of Breg cells.

pMHC-NP therapy for the suppression of liver autoimmunityFig.1 pMHC-NP therapy for the suppression of liver autoimmunity (Umeshappa C S, et al., 2021)

pMHC-NPs Development Solutions

We try to develop pMHC-NPs by displaying antigenic epitopes from various liver autoimmune disease-associated antigens and verify whether various drugs can broadly attenuate liver autoimmunity for therapeutic purposes. We provide solutions for the development and validation of pMHC-based nanomedicines for specific client projects, exploring epitopes from various liver autoimmune disease-associated antibodies, and advancing therapeutic development for liver autoimmune diseases.

Table 1. Materials and methods of pMHC-NPs development

Materials Methods
pMHC and Peptide Cell lines, peptides Reconstitute pMHC-like monomers, predict epitopes, peptide synthesis, chromatographic purification
pMHC-NP Synthesis pMHC complexes, PFM-NPs Synthesize NPs, assemble and purify pMHC-NPs, quality control
pMHC-NP Treatment NOD mouse models, cell lines Evaluate histopathology of the liver, assess general adaptive immunity, measure cytokine secretion, assess histology and immunohistochemistry, other tests and statistical analysis.

The general protocol is shown above, and depending on your specific project, we will do detailed planning and protocols.

Creative BioMart offers therapeutic development services for a variety of autoimmune diseases including but not limited to liver immune diseases, diabetes, allergies, etc. through antigen-specific NP strategies that directly target T cells. We aim to provide technology and solutions to your project to accelerate its application, please contact us to discuss the details.

References

  • Umeshappa C S, et al. "Liver-specific T regulatory type-1 cells program local neutrophils to suppress hepatic autoimmunity via CRAMP." Cell Reports (2021),34(13):108919.
  • Umeshappa C S, et al. "Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines." Nature Communications (2019),10,2150.
For research use only. Not for clinical use.
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