Use of liposomes in a carrier comprising a continuous hydrophobic phase as a vehicle for cancer treatment
The invention compositions comprising a continuous hydrophobic phase and liposomes as a vehicle for delivery of an antigen capable of inducing a cytotoxic T lymphocyte (CTL) response and methods for their use in the treatment of cancer.
1. A method for inducing an enhanced cytotoxic T lymphocyte (CTL) response thereby treating cancer or inhibiting or preventing the growth or proliferation of cancer cells in a subject in need of cancer treatment comprising:
encapsulating at least one antigen comprising a CTL epitope and at least one T helper epitopes in liposomes;
combining said liposomes with a carrier consisting essentially of oil or a water-in-oil emulsion to form a composition; and
administering said composition to said subject.
2. The method of claim 1 , wherein the cancer is selected from the group consisting of: cervical, vulvar, melanoma, breast, lung, ovarian, multiple myeloma, B cell lymphoma, hepatoma, sarcoma, bladder, prostate cancer, thyroid, H/N tumors, colon, rectal, renal, pancreatic, gastric, adenocarcinoma, T cell leukemia, lymphosarcoma, uterine, esophageal, non-Hodgkin's lymphomas, endometrial, and RCC tumors.
3. The method of claim 1 , wherein said T helper epitope is a separate molecule from said antigen.
4. The method of claim 1 , wherein said antigen comprises said T helper epitope or wherein said antigen is fused to said T helper epitope.
5. The method of claim 1 , wherein said antigen comprises a combination of CTL epitopes.
6. The method of claim 1 , wherein said CTL epitope is derived from a tumor-associated protein.
7. The method of claim 1 , wherein said CTL epitope is derived from a virus.
8. The method of claim 1 , wherein said liposomes are freeze-dried before they are combined with said carrier.
9. The method of claim 1 , further comprising encapsulating an adjuvant in said liposomes or combining an adjuvant with said carrier.
10. The method of claim 1 wherein the oil is mineral oil, nut oil, or squalene.
11. The method of claim 1 , wherein the subject is a mammal.
12. The method of claim 1 , wherein the subject is a human.
13. The method of claim 1 , wherein the liposome comprises a phospholipid.
14. The method of claim 13 , wherein the phospholipid has at least one head group selected from phosphoglycerol, phosphoethanolamine, phosphoserine, phosphocholine and phosphoinositol.
15. The method of claim 1 , wherein the liposome comprises unesterified cholesterol.
16. The method of claim 1 , wherein the liposome comprises lipids in phospholipon 90 G.
17. The method of claim 1 , wherein the liposome comprises lipids obtained from archaebacterial bacteria.
18. The method of claim 1 , wherein the liposome comprises natural lipids, synthetic lipids, sphingolipids, ether lipids, sterols, cardiolipin, cationic lipids, or lipids modified with poly (ethylene glycol) or other polymers.
19. The method of claim 18 , wherein the synthetic lipids include fatty acid constituents selected from lauroyl, myristoyl, palmitoyl, stearoyl, arachidoyl, oleoyl, linoleoyl, and erucoyl, or combinations thereof.
20. The method of claim 1 , wherein CTL epitope is derived from human papilloma virus.
21. The method of claim 1 , wherein the CTL epitope is an epitope of an E6 or E7 protein of human papilloma virus (HPV).
22. The method of claim 21 , wherein the E6 epitope comprises the peptide sequence TIHDIILECV (T10V; SEQ ID NO: 5).
23. The method of claim 1 , wherein the antigen comprises a plurality of CTL epitopes linked to form a single polypeptide.
24. The method of claim 6 , wherein the tumor associated protein is p53.
25. The method of claim 24 , wherein the tumor-associated protein is tyrosinase-related protein-2(TRP-2).
26. The method of claim 1 , wherein the antigen comprises a p53 epitope and a TRP-2 epitope.
27. The method of claim 26 , wherein the p53 epitope comprises the peptide sequence KYICNSSCM (mK9M) (SEQ ID NO: 8).
28. The method of claim 26 , wherein the TRP-2 epitope comprises the peptide sequence SVYDFFVWL (SEQ ID NO: 7) or the peptide sequence VYDFFVWL (SEQ ID NO: 6).
29. The method of claim 1 , wherein the T helper epitope is a universal T helper epitope, PADRE (pan-DR epitope) (SEQ ID NO: 10), or F21E (SEQ ID NO: 11).
30. The method of claim 1 , wherein the T helper epitope is fused to the at least one antigen.
31. The method of claim 9 , wherein the adjuvant is a CpG oligodeoxynucleotide (CpG ODN) a lipopeptide, or Pam3Cys-SKKKK.
32. A method for inducing an enhanced cytotoxic T lymphocyte (CTL) response thereby treating cancer or inhibiting or preventing the growth or proliferation of cancer cells in a subject in need of cancer treatment comprising administering a composition comprising:
a carrier consisting essentially of oil or a water-in-oil emulsion;
liposomes;
at least one antigen comprising a CTL epitope; and
at least one T helper epitope;
wherein the antigen and the T helper epitope are encapsulated within said liposomes.
33. The method of claim 32 , wherein the cancer is selected from the group consisting of: cervical, vulvar, melanoma, breast, lung, ovarian, multiple myeloma, B cell lymphoma, hepatoma, sarcoma, bladder, prostate cancer, thyroid, H/N tumors, colon, rectal, renal, pancreatic, gastric, adenocarcinoma, T cell leukemia, lymphosarcoma, uterine, esophageal, non-Hodgkin's lymphomas, endometrial, and RCC tumors.
34. The method of claim 32 , wherein said T helper epitope is a separate molecule from said antigen.
35. The method of claim 32 , wherein said antigen comprises said T helper epitope or wherein said antigen is fused to said T helper epitope.
36. The method of claim 32 , wherein said antigen comprises a combination of CTL epitopes.
37. The method of claim 32 , wherein said CTL epitope is derived from a tumor-associated protein.
38. The method of claim 32 , wherein said CTL epitope is derived from a virus.
39. The method of claim 32 , wherein said liposomes are freeze-dried before they are combined with said carrier.
40. The method of claim 32 , further comprising encapsulating an adjuvant in said liposomes or combining an adjuvant with said carrier.
41. The method of claim 32 , wherein the subject is a mammal.
42. The method of claim 32 , wherein the subject is a human.
43. The method of claim 32 , wherein the liposome comprises a phospholipid.
44. The method of claim 43 , wherein the phospholipid has at least one head group selected from phosphoglycerol, phosphoethanolamine, phosphoserine, phosphocholine and phosphoinositol.
45. The method of claim 32 , wherein the liposome comprises unesterified cholesterol.
46. The method of claim 32 , wherein the liposome comprises lipids in phospholipon 90 G.
47. The method of claim 32 , wherein the liposome comprises lipids obtained from archaebacterial bacteria.
48. The method of claim 32 , wherein the liposome comprises natural lipids, synthetic lipids, sphingolipids, ether lipids, sterols, cardiolipin, cationic lipids, or lipids modified with poly (ethylene glycol) or other polymers.
49. The method of claim 48 , wherein the synthetic lipids include fatty acid constituents selected from lauroyl, myristoyl, palmitoyl, stearoyl, arachidoyl, oleoyl, linoleoyl, and erucoyl, or combinations thereof.
50. The method of claim 32 , wherein CTL epitope is derived from human papilloma virus.
51. The method of claim 32 , wherein the CTL epitope is an epitope of an E6 or E7 protein of human papilloma virus (HPV).
52. The method of claim 51 , wherein the E6 epitope comprises the peptide sequence TIHDIILECV (T10V; SEQ ID NO: 5).
53. The method of claim 32 , wherein the antigen comprises a plurality of CTL epitopes linked to form a single polypeptide.
54. The method of claim 37 , wherein the tumor associated protein is p53.
55. The method of claim 54 , wherein the tumor-associated protein is tyrosinase-related protein-2 (TRP-2).
56. The method of claim 32 , wherein the antigen comprises a p53 epitope and a TRP-2 epitope.
57. The method of claim 56 , wherein the p53 epitope comprises the peptide sequence KYICNSSCM (mK9M) (SEQ ID NO: 8).
58. The method of claim 56 , wherein the TRP-2 epitope comprises the peptide sequence SVYDFFVWL (SEQ ID NO: 7) or the peptide sequence VYDFFVWL (SEQ ID NO: 6).
59. The method of claim 32 , wherein the T helper epitope is a universal T helper epitope, PADRE (pan-DR epitope) (SEQ ID NO: 10), or F21E (SEQ ID NO: 11).
60. The method of claim 32 , wherein the T helper epitope is fused to the at least one antigen.
61. The method of claim 40 , wherein the adjuvant is a CpG oligodeoxynucleotide (CpG ODN) a lipopeptide, or Pam3Cys-SKKKK.