There is a considerable need for targeted technologies that direct the immune system for the controlled suppression of localized inflammation. Programming immune cell metabolism is a new and active area of investigation with numerous diverse immunotherapy applications. We are developing an innovative new approach of locally administering a tissue-targeted chimeric enzyme which catabolize the essential amino acid, tryptophan, and produces kynurenines, together inducing a powerful immunosuppressive metabolic programming. The chosen tissue targeting domain confers prolonged tissue retention, and the enzymatic activity can block local inflammation for an extended time. We are applying this technology for the amelioration of periodontal disease, in which localized non-resolving chronic inflammation is associated with a shift away from a submucosal environment rich in tolerance toward one of inflammation consisting of Th1 and Th17 T cells at the expense of regulatory T cells.
Periodontal diseases, lacking effective therapeutics, are localized non-resolving chronic inflammatory diseases associated with a shift away from an environment rich in tolerance toward one of inflammation. We are developing an innovative new approach of administering an enzyme which supplies a powerful local immunosuppressive program. We have designed a targeted version of this enzyme capable of being retained, and which can block local inflammation for a prolonged period, and we are applying this technology for the amelioration of periodontal disease.
| Farhadi, Shaheen A; Bracho-Sanchez, Evelyn; Fettis, Margaret M et al. (2018) Locally anchoring enzymes to tissues via extracellular glycan recognition. Nat Commun 9:4943 |
| Farhadi, Shaheen A; Bracho-Sanchez, Evelyn; Freeman, Sabrina L et al. (2018) Enzymes as Immunotherapeutics. Bioconjug Chem 29:649-656 |
| Fernando, Lawrence P; Lewis, Jamal S; Evans, Brian C et al. (2018) Formulation and characterization of poly(propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles for pH-dependent membrane disruption and cytosolic delivery. J Biomed Mater Res A 106:1022-1033 |
