Methods of screening for immuno-adjuvants and vaccines comprising anti-microtubule immuno-adjuvants

• US 20070059319A1
• Filed: 09/11/2006
• Published: 03/15/2007
• Est. Priority Date: 09/15/2005
• Status: Abandoned Application

• Current Assignee: Novascreen Biosciences Corporation (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Carlson, Peter, Miagkov, Alexei, Widra, Martha
• Application Number:
  US11/518,522
• Publication Number:
  US 20070059319A1
• Time in Patent Office: Days
• US Class Current: 424/185.100
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: G01N 33/5047 Cells of the immune system

Abstract

A method of screening for agents that stimulate the innate immune system in mammals employs markers that respond to Toll-like receptor binding. Agents identified in the assay boost both innate and adaptive immune responses, when administered alone or in combination with vaccines.

Claims

1. A method of screening for agents that stimulate the innate immune system in a mammal, comprising:

(a) bringing a candidate agent into contact with a cellular component of said innate immune system,

(b) testing said cellular component for the level of one or more markers associated with stimulation of said innate immune system, and

(c) correlating said level with a probability that said candidate agent stimulates said innate immune system.

2. The method according to claim 1, wherein said cellular component is selected from the list consisting of a monocyte, a dendritic cell, a macrophage, a B-cell and a natural killer cell.

3. The method according to claim 2, wherein said cellular component is a monocyte.

4. The method according to claim 3, wherein said cellular component is a THP-1 cell.

5. The method according to claim 1, wherein said marker is an antigen presenting molecule of the major histocompatibility complex.

6. The method according to claim 1, wherein said marker is a costimulatory molecule.

7. The method according to claim 6, wherein said costimulatory molecule is selected from the group consisting of CD80 (B7-1), CD40 and CD54 (ICAM-1).

8. The method according to claim 1, wherein said marker is a cytokine.

9. The method according to claim 8, wherein said cytokine is selected from the group consisting of TNFA, IL-8, IL-6, MCP-1, MIP-1α

MIP-1β

, RANTES, IP-10 and MIG.

10. The method according to claim 9, wherein said cytokine is selected from the group consisting of TNFα

, IL-8, and RANTES.

11. The method according to claim 1, wherein said mammal is a human.

12. The method according to claim 1, wherein said one or more markers is a panel of markers.

13. The method according to claim 12, wherein said panel of markers comprises, CD80, CD54, IL-8, RANTES, and TNFα

.

14. A method of stimulating the innate immune system in a mammal, comprising administering a vaccine and a microtubule depolymerizing agent to said mammal.

15. The method according to claim 14, wherein said microtubule depolymerizing agent is selected from the list consisting of colchicine, vinblastine, vincristine, and demecolcine.

16. The method according to claim 14, wherein said microtubule depolymerizing agent is a component of said vaccine.

17. The method according to claim 14, wherein said microtubule depolymerizing agent is administered prior to said vaccine.

18. The method according to claim 14, wherein said microtubule depolymerizing agent is administered subsequent to said vaccine.

19. The method according to claim 14, wherein said microtubule depolymerizing agent is administered concurrently with said vaccine.

20. The method according to claim 14, wherein said mammal is a human.

21. A method of stimulating the innate immune system in a mammal, comprising:

(a) selecting a mammal in need of increased innate immunity that does not have a cell proliferative disorder, and

(b) administering a microtubule depolymerizing agent to said mammal.

22. The method according to claim 21, wherein said microtubule depolymerizing agent is selected from the list consisting of colchicine, vinblastine, vincristine, and demecolcine.

23. The method according to claim 21, wherein said cell proliferative disorder is cancer.

24. The method according to claim 21, wherein said mammal is a human.

25. A vaccine that comprises a microtubule depolymerizing agent.

26. The vaccine of claim 28, wherein said microtubule depolymerizing agent is selected from the list consisting of colchicine, vinblastine, vincristine, and demecolcine.