Microbes can be genetically modified to express biomolecules that are beneficial to mammals and/or to reduce, or eliminate, expression of harmful virulence factors. The growth and viability of such genetically modified microbes can optionally be controlled by inducible promoters that regulate the expression of proteins that are essential to their growth and survival. Compositions comprising such genetically modified microbes as well as methods of making and using the same are disclosed herein.

A composition useful for alleviating or treating pain and uses thereof are disclosed. The composition containing glutamate decarboxylase and a gene coding for an anti-inflammatory cytokine. A method for alleviating or treating pain of a subject includes administering the composition to the subject.

The present disclosure provides fusion proteins comprising an IL-10 polypeptide and a second polypeptide, e.g., an Fc polypeptide. Certain aspects of the present disclosure are directed to methods of treating a subject comprising administering the IL-10 fusion protein. In certain aspects, the subject is afflicted with a cancer.

Microorganisms are provided, such as lactic acid bacteria (e.g., Lactococcus lactis) containing an exogenous nucleic acid encoding an IL-10 polypeptide and an exogenous nucleic acid encoding a CeD-specific antigen (e.g., a gliadin polypeptide comprising at least one HLA-DQ2 specific epitope, at least one deamidated HLA-DQ2 specific epitope, at least one HLA-DQ8 specific epitope, at least one deamidated HLA-DQ8 specific epitope, or a combination of (a) at least one HLA-DQ2-specific epitope and/or at least one deamidated HLA-DQ2 specific epitope, and (b) at least one HLA-DQ8 specific epitope and/or at least one deamidated HLA-DQ8 specific epitope) polypeptide, wherein both exogenous nucleic acids are integrated into the bacterial chromosome. Such microbial strains are suitable for human therapy. Compositions (e.g., pharmaceutical compositions), methods of using the microorganisms and compositions are provided, e.g., for the treatment of celiac disease (CeD). The microorganism may be administered orally, delivering the microorganism into the gastrointestinal tract, where it is released and expresses the bioactive polypeptides.

Microorganisms are provided, such as lactic acid bacteria (e.g., Lactococcus lactis) containing an exogenous nucleic acid encoding an IL-10 polypeptide and an exogenous nucleic acid encoding a CeD-specific antigen (e.g., a gliadin polypeptide comprising at least one HLA-DQ2 specific epitope, at least one deamidated HLA-DQ2 specific epitope, at least one HLA-DQ8 specific epitope, at least one deamidated HLA-DQ8 specific epitope, or a combination of (a) at least one HLA-DQ2-specific epitope and/or at least one deamidated HLA-DQ2 specific epitope, and (b) at least one HLA-DQ8 specific epitope and/or at least one deamidated HLA-DQ8 specific epitope) polypeptide, wherein both exogenous nucleic acids are integrated into the bacterial chromosome. Such microbial strains are suitable for human therapy. Compositions (e.g., pharmaceutical compositions), methods of using the microorganisms and compositions are provided, e.g., for the treatment of celiac disease (CeD). The microorganism may be administered orally, delivering the microorganism into the gastrointestinal tract, where it is released and expresses the bioactive polypeptides.

This disclosure features methods and compositions for treating diseases of the gastrointestinal tract with IL-10 or an IL-10 agonist.

The disclosure provides, among other things, methods and uses for treating a disease or disorder, particularly tumors of a cancer patient, comprising conjointly administering effective amounts of a STING agonist, a cytokine, and an optional immune checkpoint inhibitor to the patient, wherein the STING agonist or the cytokine is intratumorally administered to the patient.

The disclosure provides, among other things, methods and uses for treating a disease or disorder, particularly tumors of a cancer patient, comprising conjointly administering effective amounts of a STING agonist, a cytokine, and an optional immune checkpoint inhibitor to the patient, wherein the STING agonist or the cytokine is intratumorally administered to the patient.

The invention relates to mutations and alterations in the inflammatory pathway, including IL-18BP and IL-10RB mutations, that are associated with the development of fulminant viral hepatitis following viral infection, such as following hepatitis virus infection. The invention relates to methods for treating or ameliorating viral hepatitis comprising administering IL-18BP, IL-18 antagonist, IFNγ antagonist or inhibitor, and/or IL-10RB or an IL-10 antagonist.

This invention provides compositions and methods for preventing inflammatory diseases of the joints, including rheumatoid and osteoarthritis, tendonitis, bursitis, inflammation of the ligament, synovitis, gout, and systemic lupus erythematosus, wherein the methods include injecting into the inflamed joint a therapeutic anti-inflammatory composition comprising a bacterial or viral IL-10 expression construct, wherein the IL-10 expression construct comprises a bacterial or viral backbone and a nucleic acid sequence encoding interleukin-10.