Use of Toll-Like Receptor agonist for treating cancer

• US 9,376,473 B2
• Filed: 01/10/2012
• Issued: 06/28/2016
• Est. Priority Date: 01/10/2011
• Status: Active Grant

• Current Assignee: Cleveland BioLabs, Inc. (Statera Biopharma, Inc.)
• Original Assignee: Cleveland BioLabs, Inc. (Statera Biopharma, Inc.)
• Inventors: Gleiberman, Anatoli, Burdelya, Lyudmila, Gudkov, Andrei
• Primary Examiner(s): Bunner, Bridget E
• Application Number:
  US13/979,104
• Publication Number:
  US 20140248260A1
• Time in Patent Office: 1,631 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/164 from bacteria
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/02 Bacterial antigens
• CPC Class Codes: A61K 39/0275 Salmonella
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: C07K 14/195 : from bacteria
• CPC Class Codes: C07K 14/255 : Salmonella (G)
• CPC Class Codes: C07K 14/705 : Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/2878 : against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95

Abstract

The present invention is directed to methods and agents used for treating cancer in Toll-Like Receptor 5-expressing tissues by providing a Toll-Like Receptor agonist such as flagellin. The present invention also relates to protecting the liver from a liver toxicity using a Toll-like receptor agonist.

Claims

1. A method of treating a cancer that does not express Toll-Like Receptor 5 (TLR5) in a subject in need thereof, comprising administering to the subject an effective amount of a TLR5 agonist,

wherein the cancer is present in a liver tissue that expresses TLR5, and

wherein the TLR5 agonist is flagellin or a flagellin derivative.

2. The method of claim 1, wherein the cancer is metastatic.

3. The method of claim 2, wherein the metastatic cancer is selected from melanoma, colon, breast, prostate, or a hematological malignancy.

4. The method of claim 3, wherein the hematological malignancy is lymphoma.

5. The method of claim 1, wherein the cancer is a tumor.

6. The method of claim 1, wherein the TLR agonist is administered as a monotherapy.

7. The method of claim 1, wherein the subject is not receiving a combination cancer therapy.

8. The method of claim 1, wherein the subject is not receiving chemotherapy or radiation therapy.

9. The method of claim 1, wherein the subject has sufficient innate immunity.

10. The method of claim 9, wherein the sufficient innate immunity level is equivalent to the level required for eligibility for a first or subsequent round of chemotherapy.

11. The method of claim 1, wherein the subject has a white blood cell count that is within the clinically normal range.

12. The method of claim 1, wherein the TLR5 agonist is administered to the subject before, after, or concurrent with removal of a tumor.

13. The method of claim 1, wherein the TLR5 agonist is co-administered with a FAS agonist.

14. The method of claim 13, wherein the FAS agonist is a FAS agonist antibody.

15. The method of claim 1, wherein the flagellin derivative comprises the amino acid sequence of SEQ ID NO:

8.

16. A method of reducing recurrence of a cancer that does not express Toll-Like Receptor 5 (TLR5) in a subject in need thereof, comprising administering to the subject an effective amount of a TLR5 agonist,

wherein the cancer is present in a liver tissue that expresses TLR5, and

wherein the TLR5 agonist is flagellin or a flagellin derivative.

17. The method of claim 16, wherein the cancer recurrence is selected from a metastasis or a tumor regrowth.

18. The method of claim 16, wherein the flagellin derivative comprises the amino acid sequence of SEQ ID NO:

8.

19. A method of treating a metastatic cancer that does not express Toll-Like Receptor 5 (TLR5) but is present in a liver tissue that expresses TLR5, comprising administering an effective amount of a flagellin or a flagellin derivative to a subject in need thereof.

20. The method of claim 19, wherein the flagellin derivative comprises the amino acid sequence of SEQ ID NO:

8.