Multivalent entrain-and-amplify immunotherapeutics for carcinoma
View Patent ↗The present invention provides a method of treating a cell proliferative disease such as cancer by providing to a subject in need thereof an immunogenic composition comprising plasmid and peptide(s) or analogues thereof. In embodiments of the present invention there is provided methods and compositions for inducing, entraining, and/or amplifying the immune response to MHC class-I restricted epitopes of carcinoma antigens to generate an effective anti-cancer immune response.
1. An immunogenic product comprising a plurality of compositions comprising one or more nucleic acid compositions and one or more peptide compositions; wherein the one or more nucleic acid compositions are capable of expressing two or more class I MHC restricted epitopes, wherein the two or more class I MHC restricted epitopes comprise a PRAME epitope and a PSMA epitope, wherein the PRAME epitope is selected from PRAME 425-433 (SEQ ID NO. 3) or a cross-reactive analogue thereof, and wherein the PSMA epitope is selected from PSMA 288-297 (SEQ ID NO. 4) or a cross-reactive analogue thereof, and wherein the one or more peptide compositions comprise one or more class I MHC restricted epitopes, wherein the one or more class I MHC restricted epitopes comprise the PRAME epitope or the PSMA epitope or both, and wherein PRAME epitope is selected from PRAME 425-433 (SEQ ID NO. 3) or a cross reactive analogue thereof and the PSMA epitope is selected from PSMA 288-297 (SEQ ID NO. 4) or a cross reactive analogue thereof.
2. The immunogenic product of claim 1 wherein said one or more nucleic acid compositions comprise the pRP12 plasmid (SEQ ID NO. 21).
3. The immunogenic product of claim 1 wherein said one or more cross-reactive analogues is selected from the group consisting of S(Nva)LQHLIG(Nle) (SEQ ID NO. 7) and GLPSIPVHPV (SEQ ID NO. 8).
4. The immunogenic product of claim 1 wherein said plurality of compositions comprise:
a) a nucleic acid molecule capable of expressing a PRAME 425-433 (SEQ ID NO. 3) class I MHC restricted epitope, or a cross-reactive analogue thereof;
b) a nucleic acid molecule capable of expressing a PSMA 288-297 (SEQ ID NO. 4) class I MHC restricted epitope, or a cross-reactive analogue thereof;
c) a peptide consisting essentially of said PRAME 425-433 (SEQ ID NO. 3) epitope, or a cross-reactive analogue thereof; and
d) a peptide consisting essentially of said PSMA 288-297 (SEQ ID NO. 4) epitope, or a cross-reactive analogue thereof.
5. The product of claim 4 wherein the nucleic acid molecules of a) and b) are part of the same composition.
6. The product of claim 5 wherein the nucleic acid molecules are the same.
7. The product of claim 6 wherein the nucleic acid molecule comprises a sequence encoding the liberation sequence of pRP12 (SEQ ID NO. 14).
8. The product of claim 7 wherein the nucleic acid comprises a sequence encoding the immunogenic polypeptide of pRP12 (SEQ ID NO. 17).
9. The product of claim 7 wherein the nucleic acid molecule is pRP12 (SEQ ID NO. 21).
10. The product of claim 4 wherein said PRAME analogue in c) is S(Nva)LQHLIG(Nle) (SEQ ID NO. 7).
11. The product of claim 4 wherein said PSMA analogue in d) is GLPSIPVHPV (SEQ ID NO. 8).
12. The immunogenic product of claim 1 wherein said plurality of compositions further comprise:
a) a nucleic acid molecule capable of expressing an SSX-2 class I MHC restricted epitope, or analogue thereof;
b) a nucleic acid molecule capable of expressing an NY-ESO-1 class I MHC restricted epitope, or analogue thereof;
c) a peptide consisting essentially of said SSX-2 epitope, or analogue thereof;
d) a peptide consisting essentially of said NY-ESO-1 epitope, or analogue thereof.
13. The product of claim 12 wherein the nucleic acid molecules of a) and b) are part of the same composition.
14. The product of claim 13 wherein the nucleic acid molecules are the same.
15. The product of claim 14 wherein the nucleic acid molecule comprises a sequence encoding the liberation sequence of pBPL(SEQ ID NO. 13).
16. The product of claim 14 wherein the nucleic acid comprises a sequence encoding the immunogenic polypeptide of pBPL (SEQ ID NO. 16).
17. The product of claim 16 wherein the nucleic acid molecule is pBPL (SEQ ID NO. 20).
18. The product of claim 12 wherein the SSX-2 epitope is SSX-2 41-49 (SEQ ID NO. 1).
19. The product of claim 12 wherein the NY-ESO-1 epitope is NY-ESO-1 157-165 (SEQ ID NO. 2).
20. The product of claim 12 wherein said SSX-2 analogue in c) is KVSEKIFYV (SEQ ID NO. 5).
21. The product of claim 12 wherein said NY-ESO-1 analogue in d) is S(Nva)LMWITQV (SEQ ID NO. 6).
22. The immunogenic product of claim 1 wherein said plurality of compositions further comprises:
i) a nucleic acid molecule capable of expressing a Melan-A class I MHC restricted epitope, or analogue thereof;
ii) a nucleic acid molecule capable of expressing a Tyrosinase class I MHC restricted epitope, or analogue thereof;
iii) a peptide consisting essentially of said Melan-A epitope, or analogue thereof; and
vi) a peptide consisting essentially of said Tyrosinase epitope, or analogue thereof.
23. The product of claim 22 wherein the nucleic acid molecules of i) and ii) are part of the same composition.
24. The product of claim 23 wherein the nucleic acid molecules are the same.
25. The product of claim 24 wherein the nucleic acid molecule comprises a sequence encoding the liberation sequence of pSEM (SEQ ID NO. 15).
26. The product of claim 25 wherein the nucleic acid comprises a sequence encoding the immunogenic polypeptide of pSEM (SEQ ID NO. 18).
27. The product of claim 26 wherein the nucleic acid molecule is pSEM.
28. The product of claim 22 wherein the Melan-A epitope is Melan-A 26-35 (SEQ ID NO. 9).
29. The product of claim 22 wherein the Tyrosinase epitope is Tyrosinase 369-377 (SEQ ID NO. 10).
30. The product of claim 22 further comprising:
i) a nucleic acid molecule capable of expressing an SSX-2 class I MHC restricted epitope, or analogue thereof; and
ii) a nucleic acid molecule capable of expressing an NY-ESO-1 class I MHC restricted epitope, or analogue thereof.
31. The product of claim 30 further comprising a peptide consisting essentially of an NY-ESO-1 epitope.
32. The product of claim 30 or 31 further comprising a peptide consisting essentially of an SSX-2 epitope.
33. The product of claim 22 wherein said Melan-A analogue in iii) is E(Nva)AGIGILTV (SEQ ID NO. 11).
34. The product of claim 22 wherein said Melan-A analogue in i) or iii) is the A27L analogue of the Melan-A 26-35 (SEQ ID NO. 9).
35. The product of claim 22 wherein said Tyrosinase analogue in iv) is YMDGTMSQ(Nva) (SEQ ID NO. 12).
36. A method of treating cancer comprising administering the product of claim 1 to a patient in need thereof.
37. The method of claim 36 , wherein the cancer is a breast cancer, an ovarian cancer, a pancreatic cancer, a prostate cancer, a colon cancer, a bladder cancer, a lung cancer, a liver cancer, a stomach cancer, a testicular cancer, an uterine cancer, a brain cancer, a lymphatic cancer, a skin cancer, a bone cancer, a kidney cancer, a rectal cancer, a melanoma, a glioblastoma, or a sarcoma.