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Compositions and methods for inhibiting shiga toxin and shiga-like toxin

A technology for bacterial toxins and fusion polypeptides, applied in the field of compositions including fusion polypeptides, can solve problems such as differences in the interaction of cellular functions and host immune systems

Inactive Publication Date: 2011-04-13
RECOPHARMA AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are similarities between Shiga toxins and Shiga-like toxins, there are some differences in their cellular functions and interactions with the host immune system

Method used

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  • Compositions and methods for inhibiting shiga toxin and shiga-like toxin
  • Compositions and methods for inhibiting shiga toxin and shiga-like toxin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Example 1: Design of Stable Cell Lines Secreting P-selectin Glycoprotein Ligand-1 The immunoglobulin G Fc fusion protein, the P-selectin glycoprotein ligand carrying Galα4Galβ3GalNacα and / or Galα4Galβ4glcnac glycans

[0072] The P-selectin glycoprotein ligand 1 (PSGL-I) / mIgG2b expression plasmid is stably transfected into the cabbage armyworm insect cells, thereby producing the required antigenic determinant Galα4Galβ3GalNAcα, and the cabbage armyworm insect cells Has endogenous α1,4 galactosyltransferase activity.

[0073] Alternatively, the P-selectin glycoprotein ligand 1 (PSGL-I) / mIgG2b expression plasmid together with α1,4-galactosyltransferase and core 2β1,6-N-acetylglucosamine-mannosyltransferase Transfected into CHO-K1 cells to generate Galα4Galβ4GlcNAc (blood group P1 epitope) construct. Alternatively, the P-selectin glycoprotein ligand 1 (PSGL-I) / mIgG2b expression plasmid is combined with α-1,4-galactosyltransferase, one or more than one peptide GaINAcTs...

Embodiment 2

[0084] Embodiment 2: Inhibition of bacterial toxin infection in vitro

[0085] Shiga toxin and / or shiga-like toxin and endothelial cells sensitive to the cytopathic effects of Shiga toxin and / or shiga-like toxin are For evaluating the inhibitory ability of the above fusion proteins with respect to the prevention of toxin-cell surface binding and aberrant protein synthesis in sensitive host cells.

Embodiment 3

[0086] Embodiment 3: route of administration

[0087] Recombinant P-selectin glycoprotein ligand 1 (PSGL-I) / mIgG2b carrying Galα4Galβ3GalNacα and / or Galα4Galβ4GlcNac glycans (ie, STI fusion protein) was administered systemically to prevent hemolytic uremia. The STI fusion protein is administered renally to prevent dissemination from the site of infection.

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Abstract

The present invention provides compositions and methods for treating or preventing infection by shiga toxin producing bacteria.

Description

[0001] References to related applications [0002] This non-provisional application claims priority to US Provisional Application No. 61 / 051,874, filed May 9, 2008, which is hereby incorporated by reference in its entirety. field of invention [0003] The present invention generally relates to compositions and methods for treating or preventing infections caused by bacteria capable of producing Shiga toxins and Shiga-like toxins, and in particular to compositions comprising fusion polypeptides, said fusion The polypeptides include carbohydrate epitopes capable of inhibiting Shiga toxins and Shiga-like toxins. Background technique [0004] Shiga toxin and Shiga-like toxin are composed of toxin A subunit and five carbohydrate-binding B subunits. Shiga toxin is produced by Shigella dysenteriae. The toxin binds to cells expressing Gb3 (Galα4Galβ4GlcβlCer) and inhibits protein synthesis through internalization, causing diarrhea, hemorrhagic enteritis or hemolytic uremic syndrom...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N1/15C12N1/21C12N5/10C07K14/47C07K14/705A61K38/17
CPCA61K38/00C07K2319/30C07K14/4727C07K2319/91C07K2319/32C07K14/70596C07K14/70589A61P31/04
Inventor A·古斯塔夫桑J·霍格尔森
Owner RECOPHARMA AB
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