Compositions and methods for inhibition of FOXP3

Patent metadata

Field	Value
Publication number	US-12344643-B2
Application number	US-201716464590-A
Country	US
Kind code	B2
Filing date	Dec 7, 2017
Priority date	Dec 7, 2016
Publication date	Jul 1, 2025
Grant date	Jul 1, 2025

Abstract

Provided herein are peptide-based therapeutics that target FOXP3 and methods of use thereof to decrease the immuno-suppressive effects of Tregs and inhibit immune dysregulation, while sparring inhibition of activated cytotoxic T cells, for example, in the context of anti-tumor immune responses, autoimmunity, inflammatory conditions, etc.

First claim

The invention claimed is:

1. A stapled alpha helical (SAH) peptide comprising at least 70% sequence identity to SEQ ID NO: 44 and being 31 or fewer amino acids in length, the peptide having a single hydrocarbon staple; wherein the SAH peptide is capable of inhibiting forkhead box P3 (FOX3P) oligomerization.

2. The SAH peptide of claim 1 , wherein the SAH peptide comprises 100% sequence identity to SEQ ID NO: 44.

3. The SAH peptide of claim 1 comprising one or more non-natural amino acids, modified amino acids, amino acid analogs, and/or peptoid amino acids.

4. A method of inhibiting FOXP3 oligomerization and/or function comprising administering the SAH peptide of claim 1 to a cell or subject.

5. A pharmaceutical composition comprising the SAH peptide of claim 1 .

6. A method of inhibiting FOXP3 oligomerization and/or function comprising administering the SAH peptide of claim 1 or PA thereof to a subject or cell.

7. The SAH peptide of claim 1 , wherein the peptide has at least 90% sequence identity to SEQ ID NO: 44.

8. The SAH peptide of claim 1 , wherein the SAH peptide is capable of binding to FOX3P.

9. The SAH peptide of claim 1 , wherein the SAH peptide is capable of inhibiting FOX3P homodimerization.

10. The SAH peptide of claim 1 , wherein the SAH peptide is capable of inhibiting FOX3P heterodimerization with nuclear factor of activated T cells (NFAT).

11. The SAH peptide of claim 1 , wherein the SAH peptide is non-toxic to T cells and Tregs.

12. The SAH peptide of claim 1 , wherein the SAH peptide is capable of blocking FOX3P binding to cognate DNA.

13. The SAH peptide of claim 1 , wherein the SAH peptide is capable of altering expression of FOXP3 target genes.

Assignees

• Univ Chicago
• Dana Farber Cancer Inst Inc

Inventors

• Labelle James
• Eclov Rachel
• Bird Gregory
• Walensky Loren D

Classifications

• C07K14/70514

  CD4 · CPC title

• C07K1/1077

  by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/4713 Primary

  Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens · CPC title