CPC A61K 35/747 (2013.01) [A61K 35/744 (2013.01); A61K 35/745 (2013.01); A61K 39/3955 (2013.01); A61K 2039/523 (2013.01); A61K 2039/542 (2013.01); A61K 2039/545 (2013.01); A61K 2039/55533 (2013.01)] | 17 Claims |
1. A method of treating type 1 diabetes mellitus (T1D) in a mammalian subject in need thereof comprising orally administering to the mammalian subject a therapeutically effective amount of a composition comprising a genetically modified lactic acid bacterium (LAB), wherein the LAB comprises an exogenous nucleic acid encoding human interleukin-2 (hIL-2) polypeptide and an exogenous nucleic acid encoding a type 1 diabetes mellitus (T1D)-specific antigen polypeptide, wherein the T1D-specific antigen polypeptide is human proinsulin (hPINS) polypeptide,
wherein said exogenous nucleic acid encoding said hPINS polypeptide comprises a polycistronic expression unit comprising, in 5′ to 3′ order, glyceraldehyde 3-phosphate dehydrogenase gene (gapB) with its promoter, and usp45 secretion leader (SSusp45) transcriptionally and translationally coupled to the sequence encoding said hPINS polypeptide; and
wherein said exogenous nucleic acid encoding said hIL-2 polypeptide comprises a polycistronic expression unit comprising, in 5′ to 3′ order, phosphopyruvate hydratase gene (eno) with its promoter, and usp45 secretion leader (SSusp45) transcriptionally and translationally coupled to the sequence encoding the hIL-2 polypeptide.
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