Composition for treating lung cancer, particularly of non-small lung cancers (NSCLC)

Patent metadata

Field	Value
Publication number	US-9352028-B2
Application number	US-201313750664-A
Country	US
Kind code	B2
Filing date	Jan 25, 2013
Priority date	Oct 9, 2007
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably a mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal. The invention furthermore relates to a vaccine comprising the active (immunostimulatory) composition, and to the use of the active (immunostimulatory) composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of lung cancer, particularly of non-small cell lung cancers (NSCLC), preferably selected from the three main sub-types squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma, or of disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the active (immunostimulatory) composition and/or the vaccine.

First claim

The invention claimed is:

1. A kit comprising at least five different immunostimulatory compositions, wherein the at least five different immunostimulatory compositions are:
(a) an immunostimulatory composition comprising an isolated NY-ESO-1 antigen coding RNA complexed with protamine;
(b) an immunostimulatory composition comprising an isolated MAGE-C1 antigen coding RNA complexed with protamine;
(c) an immunostimulatory composition comprising an isolated MAGE-C2 antigen coding RNA complexed with protamine;
(d) an immunostimulatory composition comprising an isolated 5T4 antigen coding RNA complexed with protamine; and
(e) an immunostimulatory composition comprising an isolated Survivin antigen coding RNA complexed with protamine.

2. The kit according to claim 1 , further comprising an immunostimulatory composition comprising an isolated MUC-1 antigen coding RNA complexed with protamine.

3. The kit according to claim 1 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is mRNA.

4. The kit according to claim 1 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is monocistronic RNA.

5. The kit according to claim 1 , wherein the antigen coding RNA of said at least five different immunostimulatory compositions is monocistronic RNA.

6. The kit according to claim 3 , wherein the mRNA comprises a G/C content of the antigen coding region that is increased compared to the G/C content of a wild-type RNA encoding the antigen.

7. The kit according to claim 3 , wherein the mRNA comprises a A/U content in the environment of the ribosome binding site that is increased compared with the A/U content of a wild-type RNA encoding the antigen.

8. The kit according to claim 3 , wherein the mRNA comprises a 5′ untranslated region (5′UTR) and/or 3′ untranslated region (3′UTR) that is modified compared to a wild-type RNA encoding the antigen.

9. The kit according to claim 3 , wherein the mRNA comprises a 5′ cap structure; a poly(A) tail; a poly(C) tail; and/or a globin 3′UTR.

10. The kit according to claim 1 , wherein at least one of said at least five different immunostimulatory compositions comprises at least one adjuvant.

11. The kit according to claim 1 , wherein at least one of said at least five different immunostimulatory compositions comprises a pharmaceutically acceptable carrier.

12. A method of treating lung cancer in a subject comprising administering an effective amount of said at least five different immunostimulatory compositions of a kit according to claim 1 to the subject.

13. The method according to claim 12 , wherein the lung cancer is non-small-cell lung cancer (NSCLC).

14. The kit of claim 1 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that comprises a globin 3′ UTR.

15. The kit according to claim 1 , wherein each of said different immunostimulatory compositions comprises isolated mRNA complexed with protamine and wherein each of said different immunostimulatory compositions comprises mRNA comprising a 5′ cap structure, a poly(A) tail, a globin 3′ UTR, and a G/C content of the antigen coding region, which is increased compared to the G/C content of wild-type RNA encoding the antigen.

16. The kit according to claim 2 , wherein each of said different immunostimulatory compositions comprises isolated mRNA complexed with protamine and wherein each of said different immunostimulatory compositions comprises mRNA comprising a 5′ cap structure, a poly(A) tail, a globin 3′ UTR, and a G/C content of the antigen coding region, which is increased compared to the G/C content of wild-type RNA encoding the antigen.

17. The kit according to claim 3 , wherein the mRNA comprises a 3′UTR that does not comprise an AU-rich sequence.

18. The kit according to claim 3 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that does not comprise the sequence GAACAAG.

19. A method of treating lung cancer in a subject comprising administering an effective amount of said at least five different immunostimulatory compositions of a kit according to claim 2 to the subject.

20. A kit comprising at least five different immunostimulatory compositions, wherein the at least five different immunostimulatory compositions are:
(a) an immunostimulatory composition comprising an isolated NY-ESO-1 antigen coding RNA comprising a globin 3′ untranslated region (3′UTR);
(b) an immunostimulatory composition comprising an isolated MAGE-C1 antigen coding RNA comprising a globin 3′UTR;
(c) an immunostimulatory composition comprising an isolated MAGE-C2 antigen coding RNA comprising a globin 3′UTR;
(d) an immunostimulatory composition comprising an isolated 5T4 antigen coding RNA comprising a globin 3′UTR; and
(e) an immunostimulatory composition comprising an isolated Survivin antigen coding RNA comprising a globin 3′UTR.

21. The kit according to claim 20 , further comprising an immunostimulatory composition comprising an isolated MUC-1 antigen coding RNA comprising a globin 3′UTR.

22. The kit according to claim 20 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is mRNA.

23. The kit according to claim 20 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is monocistronic RNA.

24. The kit according to claim 20 , wherein the antigen coding RNA of said at least five different immunostimulatory compositions is monocistronic RNA.

25. The kit according to claim 22 , wherein the mRNA comprises a G/C content of the antigen coding region that is increased compared to the G/C content of a wild-type RNA encoding the antigen.

26. The kit according to claim 22 , wherein the mRNA comprises a A/U content in the environment of the ribosome binding site that is increased compared with the A/U content of a wild-type RNA encoding the antigen.

27. The kit according to claim 22 , wherein the mRNA comprises a 5′ untranslated region (5′UTR) that is modified compared to a wild-type RNA encoding the antigen.

28. The kit according to claim 22 , wherein the mRNA comprises a 5′ cap structure; a poly(A) tail; and/or a poly(C) tail.

29. The kit according to claim 22 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is complexed with one or more polycationic molecules.

30. The kit of claim 29 , wherein the one or more polycationic molecules comprise protamine.

31. The kit according to claim 20 , wherein at least one of said at least five different immunostimulatory compositions comprises at least one adjuvant.

32. The kit according to claim 20 , wherein at least one of said at least five different immunostimulatory compositions comprises a pharmaceutically acceptable carrier.

33. A method of treating lung cancer in a subject comprising administering an effective amount of said at least five different immunostimulatory compositions of a kit according to claim 20 to the subject.

34. A method of treating lung cancer in a subject comprising administering an effective amount of said at least five different immunostimulatory compositions of a kit accord

Assignees

• Curevac Gmbh
• Curevac Ag

Inventors

• Barner Marijke
• Probst Jochen
• Lander Thomas
• Hoerr Ingmar

Classifications

• A61K2039/86

  Lung · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title