Vibro-based delivery system and immune suppression

Patent metadata

Field	Value
Publication number	US-2016017007-A1
Application number	US-201414770919-A
Country	US
Kind code	A1
Filing date	Mar 11, 2014
Priority date	Mar 11, 2013
Publication date	Jan 21, 2016
Grant date	—

Abstract

Embodiments described are immunosuppressant therapeutics and compositions comprising a Vop protein derived from Vibro parahaemolyticus ; and drug delivery vehicles derived from a V. parahaemolyticus expressing a mutant VopZ protein lacking amino acid residue 38 - 62.

First claim

1 . An isolated polypeptide comprising an amino acid sequence having a percent homology of at least 90% with an amino acid sequence of SEQ. ID. NO:1, wherein the polypeptide has immunosuppression activity.

2 . The isolated polypeptide of claim 1 , wherein the polypeptide suppresses interleukin-8 (IL-8) production.

3 . The isolated polypeptide of claim 1 , wherein the polypeptide inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation.

4 . The isolated polypeptide of claim 1 , wherein the polypeptide inhibits p65 nuclear translocation.

5 . The isolated polypeptide of claim 1 , wherein the polypeptide inhibits IκBα degradation.

6 . The isolated polypeptide of claim 1 , wherein the immunosuppression activity is in response to tumor necrosis factor alpha (TNF-α) and/or interleukin-1β (IL-1β) stimulation.

7 . The isolated polypeptide of claim 1 , wherein the polypeptide is fused to a second protein or portions thereof, wherein the second protein is not a polypeptide of claim 1 , or is fused/conjugated to a therapeutic molecule.

8 .- 11 . (canceled)

12 . A vector comprising a nucleic acid encoding an isolated polypeptide of claim 1 .

13 . A cell comprising a vector of claim 12 .

14 . An immunosuppression composition comprising an isolated polypeptide claim 1 and a pharmaceutically acceptable carrier.

15 .- 19 . (canceled)

20 . A method of treating an immune system disease or disorder, or suppressing a graft-versus-host disease, in a subject comprising administering to a subject in need thereof a therapeutically effective amount of an isolated polypeptide of claim 1 .

21 . A method of treating an immune system disease or disorder, or suppressing a graft-versus-host disease, comprising administering to a subject in need thereof a therapeutically effective amount of a composition of claim 14 .

22 .- 25 . (canceled)

26 . An isolated live attenuated bacterium comprising a nucleic acid encoding a mutant VopZ protein.

27 . The isolated bacterium of claim 26 is of Vibro spp.

28 . The isolated bacterium of claim 27 is Vibro parahaemolyticus.

29 . The isolated bacterium of claim 26 , wherein the encoded VopZ protein is lacking at least the amino acid residues 38-62 of SEQ. ID. NO:1.

30 . The isolated bacterium of claim 26 , wherein the encoded VopZ protein comprising an amino acid sequence having a percent homology of at least 90% with an amino acid sequence of SEQ. ID. NO:2.

31 . A composition comprising isolated live attenuated bacteria of claim 26 and a pharmaceutically acceptable carrier.

32 .- 45 . (canceled)

46 . A delivery vehicle for introducing an extraneous protein into animal cells comprising isolated live attenuated bacteria of claim 26 .

47 .- 49 . (canceled)

Assignees

• Brigham & Womens Hospital

Inventors

• Waldor Matthew
• Zhou Xiaohui
• Gewurz Benjamin

Classifications

• C07K2319/60

  containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP] · CPC title

• C07K2319/20

  containing a tag with affinity for a non-protein ligand · CPC title

• C07K2319/31

  fusions, other than Fc, for prolonged plasma life, e.g. albumin · CPC title

• C07K2319/50

  containing protease site · CPC title

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title