Method of inducing a CTL response

• US 20090035252A1
• Filed: 05/03/2006
• Published: 02/05/2009
• Est. Priority Date: 07/10/1997
• Status: Abandoned Application

• Current Assignee: Mankind
• Original Assignee: Mankind
• Inventors: Kundig, Thomas M., Simard, John J. L.
• Application Number:
  US11/418,497
• Publication Number:
  US 20090035252A1
• Time in Patent Office: Days
• US Class Current: 424/85.200
• 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. An article of manufacture for delivering an antigen that induces a CTL response in an animal, which article comprises

a reservoir of a physiologically-acceptable, composition that is capable of inducing a CTL response to an antigen in an animal,

a pump connected to the reservoir to deliver the composition at a defined rate,

a transmission line to discharge the composition from the reservoir, and, optionally,

a delivery line connected to the transmission line, which delivery line is of a size suitable for positioning in the animal and for delivery of the composition in a manner that reaches the lymphatic system of the animal.

2. The article of claim 1, wherein the reservoir is removable from the article of manufacture or is refillable.

3. The article of claim 1, wherein the composition is capable of inducing a CTL response to only one antigen.

4. The article of claim 1, wherein the composition is capable of inducing a CTL response to more than one antigen.

5. The article of claim 1, wherein the composition further comprises a cytokine capable of enhancing a CTL response.

6. The article of claim 5, wherein the cytokine is GM-CSF, IL-12, IL-2, TNF, IFN, IL-18, IL-3, IL-4, IL-8, IL-9, IL-13, IL-10, IL-14, IL-15, G-CSF, IFN-alpha, IFN-beta, IFN-gamma, TGF-alpha, or TGF-beta.

7. The article of claim 1, wherein the antigen is a differentiation antigen, a tumor-specific multilineage antigen, an embryonic antigen, an oncogene antigen, a mutated tumor-suppressor gene antigen, or a viral antigen.

8. The article of claim 7, wherein the antigen is selected from the group consisting of MelanA (MART-I), gp100 (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, p15(58), CEA, RAGE, NY-ESO (LAGE), SCP-1, Hom/MeI-40, PRAME, p53, H-Ras, HER-2/neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigens, EBNA, human papillomavirus (HPV) antigens E6 and E7, TSP-180, MAGE-4, MAGE-5, MAGE-6, p185erbB2, p180erbB-3, c-met, nm-23H1, PSA, TAG-72-4, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, β

-Catenin, CDK4, Mum-1, p16, TAGE, PSMA, PSCA, CT7, telomerase, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, β

-HCG, BCA225, BTAA, CA 125, CA 15-3 (CA 27.29\BCAA), CA 195, CA 242, CA-50, CAM43, CD68\KP1, CO-029, FGF-5, G250, Ga733 (EpCAM), HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB/70K, NY-CO-1, RCAS1, SDCCAG16, TA-90 (Mac-2 binding protein\cyclophilin C-associated protein), TAAL6, TAG72, TLP, and TPS.

9. The article of claim 1, wherein the article is an external device and the delivering line is a catheter that is long enough for delivery to the animal subcutaneously or lymphatically.

10. The article of claim 9, wherein the catheter is long enough for delivery directly to the lymphatic system of the animal.

11. The article of claim 10, wherein the catheter is at least 20 mm in length.

12. The article of claim 10, wherein the delivery to the lymphatic system is through a lymph node of lymph vessel.

13. The article of claim 12, wherein the delivery to the lymphatic system is through an axillary or inguinal node.

14. The article of claim 1, wherein the position permitting delivery of the composition is an area of high lymphatic drainage.

15. The article of claim 14, wherein the area of high lymphatic drainage is determined by imaging lymphatic flow in the animal.

16. The article of claim 1 that is portable.

17. The article of claim 16 that is of a size suitable for portably attaching to a human.

18. The article of claim 1, wherein the pump is a roller/peristaltic pump, a syringe pump, a piston/valve pump, or a gas pressure pump.

19. The article of claim 1, wherein the pump is battery operated.

20. The article of claim 1 in combination with printed instructions for delivery of the antigen composition on a regular basis over time to maintain the antigen in the animal'"'"'s lymphatic system at a level sufficient to maintain a CTL response in the animal.

21. The article of claim 1, wherein the composition comprises a polypeptide antigen.

22. The article of claim 21, wherein the composition comprises a peptide.

23. The article of claim 21, wherein the composition is free of conventional adjuvants.

24. The article of claim 1, wherein the composition comprises a nucleic acid encoding the antigen.

25. The article of claim 1, wherein the composition comprises a non-polypeptide antigen.

26. The article of claim 1, wherein the composition comprises a microbial cell, a component of a microbial cell, or a cell extract.

27. A process for preparing a system useful for inducing a sustained CTL response in an animal needing such a response, which comprises:

placing a physiologically-acceptable, aqueous, composition that is capable of inducing a CTL response to an antigen in an animal, in a reservoir having a pump for delivering the composition at a defined rate through a transmission line to the animal.

28. The process of claim 27, wherein the composition is free of conventional adjuvants.

29. The process of claim 27, wherein the antigen is an antigen specific to a tumor or pathogen and is matched to a tumor or pathogen in the animal, and a physiologically acceptable composition capable of inducing a CTL response to the matched antigen is prepared before the composition is placed in the reservoir.