Immunostimulatory Combinations

Patent metadata

Field	Value
Publication number	US-2016129095-A1
Application number	US-201514850529-A
Country	US
Kind code	A1
Filing date	Sep 10, 2015
Priority date	Dec 30, 2002
Publication date	May 12, 2016
Grant date	—

Abstract

The present invention provides immunostimulatory combinations. Generally, the immunostimulatory combinations include a TLR agonist and a TNF/R agonist. Certain immunostimulatory combinations also may include an antigen.

First claim

What is claimed is:

1 . An immunostimulatory combination comprising:
a TLR agonist and a TNF/R agonist, each in an amount that, in combination with the other, is effective to increase a subject's immune response to an antigen.

2 . The immunostimulatory combination of claim 1 wherein the TLR agonist is an agonist of at least one of TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, or any combination of any of the foregoing.

3 . The immunostimulatory combination of claim 2 wherein the TLR agonist comprises an IRM compound or an agonist of TLR2.

4 . The immunostimulatory combination of claim 1 wherein the TLR agonist comprises an IRM compound, MALP-2, LPS, polyIC, CpG, or any combination of any of the foregoing.

5 . The immunostimulatory combination of claim 3 wherein the IRM compound comprises an imidazoquinoline amine, a tetrahydroimidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, an imidazonaphthyridine amine, a tetrahydroimidazonaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.

6 . The immunostimulatory combination of claim 1 wherein the TNF/R agonist comprises an agonist of a TNF Superfamily member.

7 . The immunostimulatory combination of claim 6 wherein the TNF/R agonist comprises an agonist of CD40 ligand, OX40 ligand, 4-1BB ligand, CD27, CD30 ligand (CD153), TNF-α, TNF-β, RANK ligand, LT-β, LT-β, GITR ligand, or LIGHT

8 . The immunostimulatory combination of claim 1 wherein the TNF/R agonist comprises an agonist of a TNFR Superfamily member.

9 . The immunostimulatory combination of claim 8 wherein the TNF/R agonist comprises an agonist of CD40, OX40, 4-1BB, CD70 (CD27 ligand), CD30, TNFR2, RANK, LT-βR, HVEM, GITR, TROY, or RELT.

10 . The immunostimulatory combination of claim 1 wherein the TNF/R agonist comprises an agonistic antibody.

11 . A method of inducing a T H 1 immune response in a subject comprising:
co-administering to the subject a TLR agonist and a TNF/R agonist, each in an amount that, when in combination with the other, is effective to induce a T H 1 immune response.

12 . The method of claim 11 wherein the TLR agonist comprises an agonist of TLR2.

13 . The method of claim 11 wherein the TLR agonist comprises an agonist of TLR9.

14 . The method of claim 11 wherein the TLR agonist comprises an agonist of TLR8.

15 . The method of claim 11 wherein the TLR agonist comprises an agonist of TLR7.

16 . The method of claim 11 further comprising co-administering an antigen in an amount effective to induce an immune response in the subject.

17 . A method of activating antigen-specific CD8 + T cells in a subject comprising:
co-administering to the subject a TLR agonist and a TNF/R agonist, each in an amount that, in combination with the other, is effective to activate antigen-specific CD8 + T cells.

18 . The method of claim 17 further comprising co-administering an antigen in an amount effective to induce an immune response in the subject.

19 . The method of claim 17 wherein activating CD8 + T cells comprises expansion of CD8 + effector T cells.

20 . The method of claim 17 wherein activating CD8 + T cells comprises generating CD8 + memory T cells.

21 . The method of claim 17 wherein the TLR agonist comprises an agonist of TLR2.

22 . The method of claim 17 wherein the TLR agonist comprises an agonist of TLR9.

23 . The method of claim 17 wherein the TLR agonist comprises an agonist of TLR8.

24 . The method of claim 17 wherein the TLR agonist comprises an agonist of TLR7.

25 . The method of claim 17 wherein the TNF/R agonist comprises an agonist of a TNF Superfamily member.

26 . The method of claim 17 wherein the TNF/R agonist comprises an agonist of a TNFR Superfamily member.

27 . The method of claim 17 wherein the TNF/R agonist comprises an agonistic antibody.

28 . A method of activating antigen-specific memory CD8 + T cells in a subject having prior exposure to an antigen, comprising:
administering to the subject the antigen in an amount effective to induce antigen-specific CD8 + memory T cells to become activated, thereby generating antigen-specific CD8 + effector T cells.

29 . The method of claim 28 further comprising co-administering a TLR agonist in an amount effective to induce antigen-specific CD8 + memory T cells to become activated, thereby generating antigen-specific CD8 + effector T cells.

30 . The method of claim 28 wherein the TLR agonist comprises an agonist of TLR2.

31 . The method of claim 28 wherein the TLR agonist comprises an agonist of TLR9.

32 . The method of claim 28 wherein the TLR agonist comprises an agonist of TLR8.

33 . The method of claim 28 wherein the TLR agonist comprises an agonist of TLR7.

34 . A method of treating a condition in a subject comprising:
co-administering to the subject a TLR agonist and a TNF/R agonist, each administered in an amount that, when in combination with the other, is effective for stimulating a cell-mediated immune response.

35 . The method of claim 34 wherein the TLR agonist comprises an agonist of TLR2.

36 . The method of claim 34 wherein the TLR agonist comprises an agonist of TLR9.

37 . The method of claim 34 wherein the TLR agonist comprises an agonist of TLR8.

38 . The method of claim 34 wherein the TLR agonist comprises an agonist of TLR7.

39 . The method of claim 34 wherein the TNF/R agonist comprises an agonist of a TNF Superfamily member.

40 . The method of claim 34 wherein the TNF/R agonist comprises an agonist of a TNFR Superfamily member.

41 . The method of claim 34 wherein the TNF/R agonist comprises an agonistic antibody.

42 . The method of claim 34 further comprising co-administering an antigen associated with the condition in an amount effective for inducing a cell-mediated immune response.

43 . The method of claim 34 wherein the condition comprises a neoplastic disease.

44 . The method of claim 43 wherein co-administering the TLR agonist and the TNF/R agonist provides prophylactic treatment.

45 . The method of claim 43 wherein co-administering the TLR agonist and the TNF/R agonist provides therapeutic treatment.

46 . The method of claim 34 wherein the condition comprises an infectious disease.

47 . The method of claim 46 wherein co-administering the TLR agonist and the TNF/R agonist provides prophylactic treatment.

48 . The method of claim 46 wherein co-administering the TLR agonist and the TNF/R agonist provides therapeutic treatment.

49 . A vaccine comprising:
a TLR agonist, a TNF/R agonist, and an antigen, each in an amount that, in combination with the others, is effective for inducing an immune response to the antigen in a subject immunized with the vaccine.

Assignees

• Dartmouth College

Inventors

• Noelle Randolph J
• Ahonen Cory L
• Kedl Ross M

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title