METHODS AND COMPOSITIONS COMPRISING CATIONIC LIPIDS FOR STIMULATING TYPE 1 INTERFERON GENES

• US 20190321321A1
• Filed: 12/05/2018
• Published: 10/24/2019
• Est. Priority Date: 12/05/2017
• Status: Active Application

• Current Assignee: PDS Biotechnology Corporation
• Original Assignee: PDS Biotechnology Corporation
• Inventors: Bedu-Addo, Frank, Conn, Greg, Gandhapudi, Siva K., Ward, Martin, Woodward, Jerold
• Application Number:
  US16/210,750
• Publication Number:
  US 20190321321A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 31/231 having one or two double bonds
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 2710/20034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

Methods and compositions for modifying type I IFN signaling pathways in a subject comprising the administration a cationic lipid to the subject are provided. The cationic lipids comprise 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), enantiomers and combinations thereof. The compositions may further comprise one or more antigenic components, wherein such components are autologous or nonautologous.

Claims

1. A method for modifying a type I IFN signaling pathway in a subject comprising the administration a cationic lipid to the mammal.

2. The method of claim 1, wherein the cationic lipid comprises 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), and combinations thereof.

3. The method of claim 2, wherein the cationic lipid comprises an enantiomer of the cationic lipid.

4. The method of claim 3, wherein the wherein the cationic lipid is 1,2-dioleoyl-3-trimethylammonium propane (DOTAP).

5. The method of claim 4, wherein the enantiomer is (R)-1,2-dioleoyl-3-trimethylammonium propane (R-DOTAP) or (S)-1,2-dioleoyl-3-trimethylammonium propane (S-DOTAP).

6. The method of claim 1, wherein the type I IFN signaling pathway is upregulated/activated.

7. The method of claim 1, wherein the type I IFN signaling pathway is down-regulated/deactivated.

8. The method of claim 6, wherein the cationic lipid comprises 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), and combinations thereof.

9. The method of claim 6, wherein the cationic lipid comprises an enantiomer of the cationic lipid.

10. The method of claim 9, wherein the enantiomer is (R)-1,2-dioleoyl-3-trimethylammonium propane (R-DOTAP) or (S)-1,2-dioleoyl-3-trimethylammonium propane (S-DOTAP).

11. The method of claim 1, further comprising an antigen.

12. The method of claim 10, further comprising an antigen.

13. The method of claim 10, wherein the T-cell response is elevated.

14. The method of claim 11, wherein antigen-specific CD8+ T cell responses are elevated.

15. A method for inducing an immunogenic response in a subject comprising the administration of a composition comprising a cationic lipid wherein the administration of the cationic lipid results in the stimulation of a type I IFN signaling pathway.

16. The method of claim 15, wherein the cationic lipid comprises 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), and combinations thereof.

17. The method of claim 16, wherein the cationic lipid comprises (R)-1,2-dioleoyl-3-trimethylammonium propane (R-DOTAP).

18. The method of claim 17, wherein the T-cell response is elevated.

19. The method of claim 18, wherein antigen-specific CD8+ T cell responses are elevated.

20. A method for treating cancer in a subject, comprising the administration of a composition comprising a cationic lipid wherein the administration of the cationic lipid results in the stimulation of a type I IFN signaling pathway.

21. The method of claim 20, wherein the cationic lipid comprises 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), and combinations thereof.

22. The method of claim 21, wherein the cationic lipid comprises (R)-1,2-dioleoyl-3-trimethylammonium propane (R-DOTAP).

23. The method of claim 20, further comprising the administration of an antigen.

24. The method of claim 23, wherein the antigen is a tumor antigen.

25. The method of claim 24, wherein the tumor antigen is HPV.