Lactococcal expression of IL-35 for treatment of disease
Inventors
Pascual, David • Maddaloni, Massimo
Assignees
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Publication Number
US-12642824-B2
Publication Date
2026-06-02
Expiration Date
Abstract
The present disclosure relates generally to therapeutic compositions comprising recombinant bacteria. Further, the disclosure elaborates upon methods of utilizing the herein described therapeutic compositions to treat autoimmune and inflammatory disease. The present teachings also relate to the disclosed recombinant bacteria and methods of producing the recombinant bacteria utilized in the compositions and methods. Further taught herein are dietary supplements and food additive compositions comprising the taught recombinant bacteria.
Core Innovation
The disclosure describes recombinant lactic acid bacteria, particularly Lactococcus lactis, expressing engineered, single-chain mammalian IL-35 comprising linked p35 and EBI3 subunits. The engineered IL-35 is described in human, murine, and canine sequence forms. The disclosure presents compositions containing these bacterial cells, the recombinant cells, and methods for producing a composition for treatment of autoimmune or inflammatory disease.
The approach encompasses oral and food-based delivery, including milk-based nutraceutical and fermented milk product forms. In a mouse collagen-induced arthritis model, oral administration associates with reduced arthritis incidence and severity, reduced joint neutrophil infiltration, reduced IFN-̧̨̣̤̥̦̭̮̯̰̱̲̳̹̺̻̼͇͈͉͍͎͓͔͕͖͙͚̃̂́̀̄̆̈̊̋̌̒̓̔̽͂̓̈́͆͊͋͌͗ͣͤͥͦͧͨͩͪͫͬͭͮͯ̕͘͜͟͢͝͞͠ͅΓ, TNF-α, and IL-17, and increased IL-10 and CD4+ regulatory T-cell responses. Food-based delivery is identified as a potentially lower-cost alternative to purified IL-35 protein.
Claims Coverage
The three independent claims cover a composition, a recombinant lactic acid bacterial cell, and a method for producing a composition for treatment of autoimmune or inflammatory disease, which together present three inventive features.
Composition containing an IL-35-expressing bacterial cell
Claim 1 covers a composition comprising a recombinant lactic acid bacterial cell that expresses engineered, single-chain mammalian IL-35 comprising one of the specified human, murine, or canine amino acid sequences.
Recombinant lactic acid bacterial cell expressing engineered IL-35
Claim 7 covers a recombinant lactic acid bacterial cell comprising a nucleotide sequence encoding engineered, single-chain mammalian IL-35 and expressing one of the specified human, murine, or canine IL-35 sequences.
Production of a composition for disease treatment
Claim 13 covers a method for producing a composition for treatment of an autoimmune or inflammatory disease, wherein the resulting recombinant lactic acid bacterial cell expresses one of the specified engineered, single-chain mammalian IL-35 sequences.
The independent claims cover the IL-35-expressing bacterial cell, a composition containing that cell, and production of a composition for autoimmune or inflammatory disease treatment. Dependent claims further specify sequence forms, Lactococcus cells, genomic integration, milk-based formulations, and treatment-associated biomarker changes.
Stated Advantages
In the mouse collagen-induced arthritis model, oral LL-IL35 is associated with reduced arthritis incidence and severity and reduced joint neutrophil infiltration.
Treatment is associated with reduced IFN-γ, TNF-α, and IL-17, alongside increased IL-10 and changes in CD4+ regulatory T-cell responses compared with controls.
Oral and food-based delivery is identified as a potentially lower-cost alternative to purified IL-35 protein.
Documented Applications
Treatment or prevention of autoimmune or inflammatory disease using a composition containing recombinant lactic acid bacteria expressing engineered, single-chain mammalian IL-35.
Oral delivery in a mouse collagen-induced arthritis model.
Food-based formulations, including milk-based nutraceuticals and fermented milk products such as yogurt, buttermilk, kefir, cheese, crème fraiche, or cultured sour cream.
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