Use of toll-like receptor agonist for treating cancer
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.
1. A method of treating a cancer present in a tissue that expresses a Toll-Like Receptor 5 (TLR5), comprising administering an effective amount of a TLR5 agonist to a subject in need thereof,
wherein the cancer does not express TLR5,
wherein the TLR5 agonist is flagellin or a flagellin derivative, and
wherein the TLR5-expressing tissue is intestinal.
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 flagellin derivative comprises the amino acid sequence of SEQ ID NO:8.
14. The method of claim 1 , wherein the TLR5 agonist upregulates chemokines, cytokines and their receptors indicative of activation of innate immunity mobilizing mechanisms.
15. 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 an intestinal tissue that expresses TLR5, and wherein the TLR5 agonist is flagellin or a flagellin derivative.
16. The method of claim 15 , wherein the cancer recurrence is selected from a metastasis or a tumor regrowth.
17. The method of claim 15 , wherein the flagellin derivative comprises the amino acid sequence of SEQ ID NO:8.
18. A method of treating a metastatic cancer that does not express Toll-Like Receptor 5 (TLR5) but is present in an intestinal tissue that expresses TLR5, comprising administering an effective amount of a flagellin or a flagellin derivative to a subject in need thereof.
19. The method of claim 18 , wherein the flagellin derivative comprises the amino acid sequence of SEQ ID NO:8.