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CN-121971599-A - Methods and compositions for treating inflammatory and autoimmune disorders with ECM-affinity peptides linked to anti-inflammatory agents

CN121971599ACN 121971599 ACN121971599 ACN 121971599ACN-121971599-A

Abstract

The present disclosure relates to collagen binding modification engineering using Collagen Binding Peptides (CBPs) and vWF A3 anti-inflammatory agents to achieve targeted treatment of inflammatory diseases. Accordingly, embodiments of the present disclosure relate to compositions comprising an anti-inflammatory agent operably linked to an extracellular matrix (ECM) affinity peptide. Cytokines and anti-inflammatory agents, such as CD200, linked to serum proteins and/or ECM affinity peptides are also disclosed. Other aspects of the disclosure relate to methods for treating an autoimmune or inflammatory disorder in a subject comprising administering to the subject a composition of the disclosure.

Inventors

  • HUBBELL JEFFREY A.
  • Namata kiyomitsu
  • Ishihara Rinka
  • SHI YUANCHUN
  • Aslan mansulov

Assignees

  • 芝加哥大学

Dates

Publication Date
20260505
Application Date
20200225
Priority Date
20190225

Claims (10)

  1. 1.A composition comprising an anti-inflammatory agent operably linked to an extracellular matrix (ECM) affinity peptide.
  2. 2. A composition comprising an anti-inflammatory agent operably linked to a serum protein.
  3. 3. The composition of claim 1, wherein the anti-inflammatory agent comprises an anti-inflammatory antibody.
  4. 4. The composition of claim 3, wherein the anti-inflammatory antibody comprises an antibody that specifically targets TNF- α, IL-1, IL-5, IL-6R, IL-12, IL-17A, IL-18, IFN- γ, GM-CSF, CD3, CD20, VLA-4, VLA-5, VCAM-1, TGF- β1, α4-integrin, α4β7-integrin, connective tissue growth factor, platelet-derived growth factor, plasminogen activator inhibitor-1, or insulin-like growth factor binding protein.
  5. 5. The composition of claim 3, wherein the antibody is a humanized or chimeric antibody.
  6. 6. The composition of claim 2, wherein the serum protein comprises albumin.
  7. 7. The composition of claim 1 or 2, wherein the anti-inflammatory agent comprises an anti-inflammatory cytokine polypeptide.
  8. 8. The composition of claim 7, wherein the cytokine polypeptide comprises polypeptides from IL-4, IL-1ra, IL-5, IL-10, IL-11, IL-23, IL-35, IL-36ra, IL-37, interferon- β, TGF- β1, TNF receptor I, and TNF receptor II.
  9. 9. A method for treating an autoimmune or inflammatory disorder in a subject, comprising administering to the subject a composition according to any one of claims 1 to 8.
  10. 10. A method for reducing inflammation in a subject, comprising administering to the subject a composition comprising an anti-inflammatory agent operably linked to an extracellular matrix (ECM) affinity peptide.

Description

Methods and compositions for treating inflammatory and autoimmune disorders with ECM-affinity peptides linked to anti-inflammatory agents The present application is a divisional application of chinese application patent application with application number 202080030419.5, 25 of the year 2020, entitled "methods and compositions for treating inflammatory and autoimmune disorders with ECM affinity peptides linked to anti-inflammatory agents". The present application claims the benefit of priority from U.S. provisional patent application No. 62/809,988, filed on 25.2.2019, the entire contents of which are incorporated herein by reference. Technical Field The present invention relates generally to the field of medicine. More particularly, it relates to compositions and methods involving nucleotide constructs and proteins, including engineered anti-inflammatory agents for targeting inflamed tissues. Background Treatment with cytokines and their receptors significantly alters the outcome of inflammatory and autoimmune diseases, particularly in anti-TNF therapy of Rheumatoid Arthritis (RA) and Inflammatory Bowel Disease (IBD) (1-5). However, the currently approved drugs do not completely cure most patients and may produce significant side effects by inhibiting systemic immunity (6-10). In order to improve the therapeutic effect and reduce systemic side effects, effective delivery of drugs to the inflamed area is a promising therapeutic strategy for such diseases. Inflammatory tissues release a range of mediators that induce enhanced osmotic retention (EPR) effects (11-12). The EPR effect is caused by the loose endothelial junctions allowing extravasation of macromolecules and non-functional lymphatic vessels, resulting in an extended residence time of macromolecules in solid tumors and inflamed tissues (11-15). Unlike tumour tissue, inflamed tissue has a functional lymphatic system from which the agents are excreted (14-16). Currently, there is no effective way to target inflamed tissue for inflammatory and autoimmune diseases due to rapid clearance from the inflamed tissue. Thus, there is a need in the art for therapies that directly target inflamed tissue. Disclosure of Invention The present disclosure relates to collagen binding modification engineering using Collagen Binding Peptides (CBPs) and vWF A3 anti-inflammatory agents to achieve targeted treatment of inflammatory diseases. Accordingly, embodiments of the present disclosure relate to compositions comprising an anti-inflammatory agent operably linked to an extracellular matrix (ECM) affinity peptide. Aspects of the disclosure also relate to anti-inflammatory agents operably linked to serum proteins and compositions comprising anti-inflammatory agents operably linked to serum proteins. Other aspects of the disclosure relate to methods for treating an autoimmune or inflammatory disorder in a subject comprising administering to the subject a composition of the disclosure. Other aspects of the disclosure relate to methods for reducing inflammation in a subject comprising administering to the subject a composition comprising an anti-inflammatory agent operably linked to an extracellular matrix (ECM) affinity peptide. In some embodiments, the inflammation is due to an autoimmune or inflammatory disorder, and wherein the autoimmune or inflammatory disorder comprises inflammatory bowel disease, idiopathic pulmonary fibrosis, multiple sclerosis, type 1 diabetes, or arthritis. In some embodiments, the anti-inflammatory agent operably linked to the ECM affinity peptide comprises a collagen binding domain conjugated to anti-tnfα. In some embodiments, the anti-inflammatory agent operably linked to the ECM affinity peptide comprises vWF-A3 operably linked to IL-4. In some embodiments, the anti-inflammatory agent operably linked to the ECM affinity peptide comprises a collagen binding domain that binds to anti-TGF- β. In some embodiments, the composition is administered systemically. In some embodiments, the composition is topically applied. In some embodiments, the dose of the anti-inflammatory agent operably linked to the ECM-affinity peptide is at least 20% less than the minimum effective dose of the anti-inflammatory agent administered topically without the peptide. In some embodiments, the anti-inflammatory agent comprises an anti-inflammatory antibody. In some embodiments, the anti-inflammatory antibody comprises an antibody specific for TNF-alpha, IL-1, IL-5, IL-6R, IL-12, IL-17A, IL-18, IFN-gamma, GM-CSF, CD3, CD20, VLA-4, VLA-5, VCAM-1, TGF-beta 1, alpha 4-integrin, alpha 4 beta 7-integrin, connective tissue growth factor, platelet derived growth factor, plasminogen activator inhibitor-1, or an insulin-like growth factor binding protein. In some embodiments, the antibody is an anti-TNF- α, anti-IL-1, anti-IL-5, anti-IL-6R, anti-IL-12, anti-IL-17A, anti-IL-18, anti-IFN- γ, anti-GM-CSF, anti-CD 3, anti-CD 20, anti-VLA-4, anti-VLA-5, anti-VCAM-1, anti-TGF- β1, anti