Method of inducing a CTL response

• US 6,977,074 B2
• Filed: 02/02/2001
• Issued: 12/20/2005
• Est. Priority Date: 07/10/1997
• Status: Expired due to Fees

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Simard, John J. L., Kündig, Thomas M.
• Primary Examiner(s): Chan, Christina
• Assistant Examiner(s): HUYNH, PHUONG N
• Application Number:
  US09/776,232
• Publication Number:
  US 20020007173A1
• Time in Patent Office: 1,782 Days
• Field of Search: 424/93.7, 424/184.1, 424/186.1, 424/190.1, 424/199.1, 424/200.1, 424/534, 435/325, 435/252, 435/5, 435/6, 435/320, 514/44, 530/300, 530/350, 530/351, 536/23.5
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• 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 38/00 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 Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2760/10022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2760/10034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Disclosed herein are methods for inducing an immunological CTL response to an antigen by sustained, regular delivery of the antigen to a mammal so that the antigen reaches the lymphatic system. Antigen is delivered at a level sufficient to induce an immunologic CTL response in a mammal and the level of the antigen in the mammal'"'"'s lymphatic system is maintained over time sufficient to maintain the immunologic CTL response. Also disclosed is an article of manufacture for delivering an antigen that induces a CTL response in an animal.

Claims

1. A method of inducing a CTL response in a mammal, which method comprises:

delivering a liquid comprising an antigen directly to a lymph node or lymph vessel of the mammal at a level sufficient to induce an antigen-specific CTL response in the mammal; and

maintaining the antigen in the mammal'"'"'s lymphatic system over time sufficient to induce the CTL response.

2. The method of claim 1, wherein the antigen is delivered directly to a lymph node.

3. The method of claim 1, wherein the antigen comprises a protein or peptide.

4. The method of claim 1, wherein the antigen is delivered in a single bolus.

5. The method of claim 1, wherein the antigen is provided as a component of a microorganism.

6. The method of claim 1, wherein the antigen is delivered in the form of a nucleic acid encoding the antigen.

7. The method of claim 6, wherein said nucleic acid is plasmid DNA in a formulation comprising about 1-10% ethyl alcohol, 0-1% benzyl alcohol, 0.25-0.5 mM EDTA and a citrate-phosphate buffer of pH 7.4-7.8, comprising about 3-50 mM citrate and about 90-200 mM phosphate.

15. The method of claim 1, wherein said delivering step further comprises delivering said liquid directly to the lymph node or lymph vessel of the mammal from a device external to the mammal.

17. The method of claim 1, wherein the antigen is delivered continuously over a period of time.

18. The method of claim 1, wherein the antigen is selected from the group consisting of a peptide, a polypeptide, a polyepitope amino acid sequence, and a protein.

19. The method of claim 1, wherein the antigen is a component or lysate of a microorganism or mammalian cell.

20. The method of claim 1, wherein the antigen is provided as a vector carrying and/or conferring expression of the antigen.

21. The method of claim 20, wherein the vector is selected from the group consisting of a bacterium, a virus, a protozoan, and a professional antigen-presenting cell.

22. The method of claim 21, wherein the vector is a dendritic cell.

29. The method of claim 1, further comprising the step of selecting a patient in need of treatment for a disease condition, wherein the CTL response is specific to an antigen associated with said condition.

30. The method of claim 1, wherein the antigen is a disease-matched antigen.

8. A method of inducing a CTL response in a mammal, which method comprises:

delivering a liquid comprising an antigen in a continuous, repeated, or sustained manner directly to a lymph node or lymph vessel of the mammal at a level sufficient to induce an antigen-specific CTL response in the mammal; and

maintaining the antigen in the mammal'"'"'s lymphatic system over time sufficient to induce the CTL response.

9. The method of claim 8, wherein induction of cytotoxic T lymphocytes is obtainable independent of immunopotentiator.

10. The method of claim 9, wherein the antigen is delivered with a cytokine.

11. The method of claim 9, wherein the antigen is delivered in the form of a nucleic acid encoding the antigen.

12. The method of claim 8, wherein the antigen is provided as a component of a microorganism cell, and wherein said microorganism cell comprises a recombinant nucleic acid encoding or promoting expression of said antigen.

13. The method of claim 8, wherein the CTL response comprises an immunological CTL response.

14. The method of claim 8, further comprising obtaining a sustained CTL response in the mammal and detecting a CTL response in the mammal.

16. The method of claim 8, wherein said delivering step further comprises delivering said liquid directly to the lymph node or lymph vessel of the mammal from a device external to the mammal.

23. The method of claim 8, wherein the antigen is selected from the group consisting of a peptide, a polypeptide, a polyepitope amino acid sequence, and a protein.

24. The method of claim 8, wherein the antigen is a component or lysate of a microorganism or mammalian cell.

25. The method of claim 8, wherein the antigen is provided as a vector carrying and/or conferring expression of the antigen.

26. The method of claim 25, wherein the vector is selected from the group consisting of a bacterium, a virus, a protozoan, and a professional antigen-presenting cell.

27. The method of claim 26, wherein the vector is a dendritic cell.

28. The method of claim 8, wherein the antigen is provided as a component of a microorganism.

31. The method of claim 8, further comprising the step of selecting a patient in need of treatment for a disease condition, wherein the CTL response is specific to an antigen associated with said condition.

32. The method of claim 8, wherein the antigen is a disease-matched antigen.