Granted Patent
B2
US 12,350,317 · App. 17/426,234 · Granted Jul 8, 2025
Immunotherapy for the treatment and prevention of inflammatory bowel disease
Inventors:
Charles O. Elson (Birmingham, AL); Wayne Duck (Pell City, AL); Qing Zhao (Birmingham, AL); Katie Alexander (Homewood, AL)
Assignee:
THE UAB RESEARCH FOUNDATION
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Abstract
Provided herein are methods and compositions for treating and preventing inflammatory bowel disease.
Claims (18)
1. A method for treating or preventing inflammatory bowel disease comprising administering to a subject having inflammatory bowel disease or at risk of developing inflammatory bowel disease
a) an effective amount of a multi-epitope polypeptide comprising two or more flagellin T-cell receptor (TCR) epitopes selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7 SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO; 27, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, and SEQ ID NO: 37; and
b) an effective amount of an agent that reduces flagellin antigen-specific memory T cells and/or increases regulatory T cells in the subject.
2. A method for delaying or reducing the intensity of a relapse or flare of an inflammatory bowel disease in a subject comprising administering to a subject
a) an effective amount of a polypeptide comprising two or more flagellin T-cell receptor (TCR) epitopes selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7 SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO; 27, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, and SEQ ID NO: 37; and
b) an effective amount of an agent that increases regulatory T cells in the subject.
3. The method of claim 1 , wherein the agent that reduces flagellin antigen-specific memory T cells and/or increases regulatory T cells in the subject is selected from the group consisting of a mutant IL-2 polypeptide selected from the group consisting of SEQ ID NO: 29 and SEQ ID NO: 30, a metabolic inhibitor and a combination thereof.
4. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
5. The method of claim 1 , wherein the two or more TCR epitopes activate flagellin-specific CD4 + T cells.
6. The method of claim 3 , wherein the metabolic inhibitor inactivates flagellin-specific activated T cells.
7. The method of claim 3 , wherein the metabolic inhibitor is an FK506-binding protein 12-rapamycin-associated protein 1 (mTOR) inhibitor.
8. The method of claim 7 , wherein the mTOR inhibitor is rapamycin.
9. The method of claim 1 , further comprising administering a protein kinase AMP-activated catalytic subunit alpha 1 (AMPK) activator to the subject.
10. The method of claim 9 , wherein the AMPK activator is metformin.
11. The method of claim 1 , wherein an increase in Treg cells and/or a decrease in memory (T M ) cells occurs in the subject.
12. The method of claim 1 , wherein the subject has an increased anti-flagellin response as compared to a control.
13. The method of claim 1 , wherein the polypeptide comprises two or more T-cell receptor (TCR) epitopes selected from the group consisting of SEQ ID NO: 6 (MVVQHNMQAMNANRMLNVTT), SEQ ID NO: 7 (LTEVHSMLQRMNELAVQASNG), SEQ ID NO: 8 (MVVQHNMTAANANRM), and SEQ ID NO: 9 (GETHSILQRMNELATQAAN).
14. The method of claim 13 , wherein the polypeptide comprises the amino acid sequences of SEQ ID NO: 5.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 31, 2021
From: ELSON, CHARLES O.; DUCK, WAYNE; ZHAO, QING; ALEXANDER, KATIE
To: THE UAB RESEARCH FOUNDATION
Reel/Frame 057971/0800 →
Continuity (2)
Provisional Application
62802873
· Feb 8, 2019
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