Therapeutically triggering an innate immune response in a target tissue
Inventors
Gunn, Harold David • Mullins, David W. • Kalyan, Shirin • Bosiljcic, Momir • Zhang, Monan Angela • Bazett, Mark • Thalen, Marcel • McGovern, Dermot • Kabakchiev, Boyko Traychev • Sham, Ho Pan
Assignees
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Publication Number
US-11226340-B2
Publication Date
2022-01-18
Expiration Date
Abstract
The invention provides therapeutic compositions that present an artificial repertoire of mammalian pattern recognition receptor (PRR) agonists, so that the pattern of PRR agonists recapitulates a distinct portion of a PRR agonist signature of a mammalian pathogen. The artificial repertoire of PRR agonists may be formulated together in a therapeutic vehicle for combined presentation to an innate immune cell resident in a target tissue in a mammalian host, and the vehicle adapted to deliver the PRR agonists to the target tissue, so as to modulate an immune response.
Core Innovation
The invention relates to improving efficacy of a site specific immunotherapy (SSI) treatment of a human patient having Crohn's disease. The SSI treatment comprises a formulation comprising a whole, killed or attenuated E. coli that is pathogenic in the gastrointestinal tract. The approach is based on measuring cytokine protein levels in serum and using those measurements to guide subsequent SSI dosing.
The method comprises measuring, or having measured, in vitro levels of two or more of IFNgamma, IL-12P70 and IL-17A protein in a serum sample from the patient undergoing the SSI treatment. Based on the measured level of IFNgamma, IL-12P70 and/or IL-17A, the method treats the patient with an adjusted dosage and/or dosage regimen of the SSI treatment. The adjustment is used to thereby increase the level of IFNgamma, IL-12P70 and/or IL-17A in a subsequent serum sample.
In refined embodiments, additional serum biomarker measurements include Eotaxin 1, GROα, IL-10, PDGF AA and/or RANTES. In some embodiments, the method includes determining that a measured level of Eotaxin 1 is below a predetermined threshold level. The method can also be applied in an anti-TNFα naïve patient, and can incorporate patient genomic detection using specific SNPs such as rs9286879 and rs751810.
Claims Coverage
The document provides one independent claim describing an SSI efficacy-improvement method for Crohn's disease. The independent claim includes a biomarker-driven adjustment of SSI dosage/regimen based on in vitro serum protein levels of IFNgamma, IL-12P70, and/or IL-17A, and thereby aims to increase these cytokine protein levels in a subsequent serum sample.
Cytokine protein-guided SSI dosage adjustment in Crohn's disease
Measuring or having measured in vitro a level of two or more of IFNgamma, IL-12P70 and IL-17A protein in a serum sample from the patient undergoing the SSI treatment; and treating the patient with an adjusted dosage and/or dosage regimen of the SSI treatment based on the measured level of IFNgamma, IL-12P70 and/or IL-17A to thereby increase the level of IFNgamma, IL-12P70 and/or IL-17A in a subsequent serum sample.
Across the claims provided, the core coverage is the use of in vitro measured serum cytokine protein levels (IFNgamma, IL-12P70, IL-17A) to adjust SSI dosing/regimen for a Crohn's disease patient receiving SSI with whole, killed or attenuated gastrointestinal-pathogenic E. coli, with additional refinements involving other serum biomarkers, threshold behavior for Eotaxin 1, anti-TNFα naïve context, and SNP/allele detection (rs9286879 and rs751810).
Stated Advantages
Increase the level of IFNgamma, IL-12P70 and/or IL-17A in a subsequent serum sample by treating the patient with an adjusted dosage and/or dosage regimen of the SSI treatment.
Improving efficacy of site specific immunotherapy (SSI) treatment for a human patient having Crohn's disease.
Documented Applications
Crohn's disease treatment using site specific immunotherapy (SSI) with a formulation comprising whole killed or attenuated E. coli pathogenic in the gastrointestinal tract.
Improving efficacy of a site specific immunotherapy (SSI) treatment in a human patient having Crohn's disease using a formulation comprising whole, killed or attenuated E. coli pathogenic in the gastrointestinal tract.
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