Method of inducing and/or enhancing an immune response to tumor antigens
An improved method of inducing and/or enhancing an immune response to a tumor antigen is disclosed. The method involves administering the tumor antigen, nucleic acid coding therefor, vectors and/or cells comprising said nucleic acid, or vaccines comprising the aforementioned to a lymphatic site.
1. A method for inducing an immune response to a tumor antigen in a human being comprising administering a tumor antigen in a first form directly into at least one lymph node and subsequently administering the tumor antigen in a second form different from the first form directly into the at least one lymph node.
2. A method according to claim 1 wherein the tumor antigen is selected from the group consisting of CEA, gp100, the MAGE family of proteins, DAGE, GAGE, RAGE, NY-ESO 1, Melan-A/MART 1, TRP-1, TRP-2, tyrosinase, HER-2/neu, MUC-1, p53, KSA, PSA, PSMA, fragments thereof and modified versions thereof.
3. A method according to claim 1 wherein at least one of said forms is a nucleic acid encoding the tumor antigen and the nucleic acid is selected from the group consisting of viral nucleic, acid, bacterial DNA, plasmid DNA, naked DNA, and RNA.
4. A method according to claim 3 wherein the viral nucleic acid is selected from the group consisting of adenoviral, alpha viral and poxviral nucleic acid.
5. A method according to claim 4 wherein the poxyiral nucleic acid selected from the group consisting of avipox, orthopox and suipox nucleic acid.
6. A method according to claim 4 wherein the poxyiral nucleic acid is selected from the group consisting of vaccinia, fowl pox, canarypox and swinepox nucleic acid.
7. A method according to claim 4 wherein the poxyiral nucleic acid is selected from the group consisting of MVA, NYVAC, TROVAC, and ALVAC nucleic acid.
8. A method according to claim 1 wherein at least one of said forms is a nucleic acid encoding the tumor antigen and the nucleic acid is contained in a vector.
9. A method according to claim 8 wherein the vector is a recombinant virus or bacteria.
10. A method according to claim 9 wherein the recombinant virus is selected from the group consisting of adenovirus, alphavirus and poxvirus.
11. A method according to claim 10 wherein the poxvirus is selected from the group consisting of avipox, orthopox and suipox.
12. A method according to claim 10 wherein the poxvirus is selected from the group consisting of vaccinia, fowlpox, canarypox and swinepox.
13. A method according to claim 10 wherein the poxvirus is selected from the group consisting of MVA, NYVAC, TROVAC, and ALVAC.
14. A method according to claim 1 wherein at least one of said forms is a nucleic acid encoding the tumor antigen and the nucleic acid is contained in a cell.
15. A method according to claim 1 wherein at least one of said forms is a nucleic acid encoding the tumor antigen and the nucleic acid is contained in a pharmaceutical composition.
16. A method according to claim 1 wherein the tumor antigen is selected from the group consisting of gp100, carcinoembryonic antigen (CEA), a fragment of gp100, a fragment of CEA, a modified version of gp100, and a modified version of CEA.
17. A method according to claim 16 wherein the modified version of gp100 comprises at least the sequence IMDQVPFSY (SEQ ID NO: 1) or the sequence YLEPGPVTV (SEQ. ID NO:2).
18. A method according to claim 16 wherein the modified version of CEA comprises SEQ ID NO:112).
19. A method according to claim 1 wherein the first form is a nucleic, acid and the second form is a peptide.
20. A method according to claim 19 wherein the tumor antigen is selected from the group consisting of CEA, gp100, the MAGE family of proteins, DACE, GAGE, RAGE, NY-ESO 1, Melan-A/MART 1, TRP-1, TRP-2, tyrosinase, HER-2/neu, MUC-1, p53, KSA, PSA, PSMA, fragments thereof, and modified versions thereof.
21. A method according to claim 19 wherein the nucleic acid is selected from the group consisting of viral nucleic acid, bacterial DNA, plasmid DNA, naked DNA, and RNA.
22. A method according to claim 21 wherein the viral nucleic acid is selected from the group consisting of adenoviral, alphaviral and poxyiral nucleic acid.
23. A method according to claim 22 wherein the poxviral nucleic acid selected from the group consisting of avipox, orthopox and suipox nucleic acid.
24. A method according to claim 23 wherein the poxyiral nucleic acid is selected from the group consisting of vaccinia, fowl pox, canarypox and swinepox nucleic acid.
25. A method according to claim 24 wherein the poxyiral nucleic acid is selected from the group consisting of MVA, NYVAC, TROVAC, and ALVAC nucleic acid.
26. The method of claim 1 wherein both a humoral and cell mediated immune response greater than that produced by subcutaneous immunization are observed.
27. The method of claim 1 wherein the tumor antigen is not co-administered with an adjuvant.
28. The method of claim 19 wherein the peptide is selected from the group consisting of SEQ ID NO.: 1, SEQ ID NO.: 2, and SEQ ID NO.: 113.
29. The method of claim 1 wherein the first form of the tumor antigen comprises SEQ ID NO.: 110.
30. The method according to claim 16 wherein the modified version of CEA comprises SEQ ID NO:113.
31. The method of claim 1 wherein the first form of the tumor antigen comprises SEQ ID NO.: 110 and the second form of the tumor antigen is at least one of the peptides SEQ ID NO.: 1 or SEQ ID NO.: 2.