Combination of vaccination and inhibition of the PD-1 pathway
The present invention relates to a vaccine/inhibitor combination comprising an RNA vaccine comprising at least one RNA comprising at least one open reading frame (ORF) coding for at least one antigen and a composition comprising at least one PD-1 pathway inhibitor, preferably directed against PD-1 receptor or its ligands PD-L1 and PD-L2. The present invention furthermore relates to a pharmaceutical composition and a kit of parts comprising the components of such a vaccine/inhibitor combination. Additionally the present invention relates to medical use of such a vaccine/inhibitor combination, the pharmaceutical composition and the kit of parts comprising such a vaccine/inhibitor combination, particularly for the prevention or treatment of tumor or cancer diseases or infectious diseases. Furthermore, the present invention relates to the use of an RNA vaccine in therapy in combination with a PD-1 pathway inhibitor and to the use of a PD-1 pathway inhibitor in therapy in combination with an RNA vaccine.
1. A method of treating a subject having a cancer or a tumor disease, the method comprising administering to the subject an effective amount of:
(i) an immunogenic composition comprising at least one mRNA comprising at least one open reading frame (ORF) encoding at least one tumor antigen; and
(ii) a PD-1 pathway inhibitor, said PD-1 pathway inhibitor comprising an antagonistic antibody directed against PD-1 or PD-L1.
2. The method of claim 1 , wherein the PD-1 pathway inhibitor comprises an antagonistic antibody directed against PD-1.
3. The method of claim 1 , wherein the PD-1 pathway inhibitor comprises an antagonistic antibody directed against PD-L1.
4. The method of claim 1 , wherein the at least one open reading frame is codon optimized for the human codon usage.
5. The method of claim 1 , wherein the at least one open reading frame of the at least one RNA comprises an increased G/C content relative to the open reading frame of a wild type RNA encoding the tumor antigen.
6. The method of claim 1 , wherein the at least one RNA is complexed with a carrier.
7. The method of claim 6 , wherein the carrier is a cationic, polycationic or polymeric carrier.
8. The method of claim 7 , wherein the carrier comprises protamine.
9. The method of claim 7 , wherein the carrier comprises a cationic or polycationic lipid.
10. The method of claim 1 , wherein the PD-1 pathway inhibitor is administered after said immunogenic composition.
11. The method of claim 1 , wherein the immunogenic composition and the PD-1 pathway inhibitor are administered sequentially.
12. The method of claim 1 , wherein the immunogenic composition and the PD-1 pathway inhibitor are administered concurrently.
13. The method of claim 12 , wherein the immunogenic composition and the PD-1 pathway inhibitor are administered in the same composition.
14. The method of claim 1 , wherein the immunogenic composition and the PD-1 pathway inhibitor are administered via different administration routes.
15. A kit of parts comprising:
(i) an immunogenic composition comprising at least one mRNA comprising at least one open reading frame (ORF) encoding at least one tumor antigen; and
(ii) a composition comprising a PD-1 pathway inhibitor, said PD-1 pathway inhibitor comprising an antagonistic antibody directed against PD-1 or PD-L1.
16. A pharmaceutical composition comprising an effective amount of: (i) at least one mRNA comprising at least one open reading frame (ORF) encoding at least one tumor antigen; and (ii) a PD-1 pathway inhibitor, said PD-1 pathway inhibitor comprising an antagonistic antibody directed against PD-1 or PD-L1.
17. The method of claim 1 , wherein the at least one mRNA is chemically modified.
18. The method of claim 17 , wherein the at least one mRNA comprises a phosphate backbone modification or sugar modification.
19. The method of claim 17 , wherein the at least one mRNA comprises a modification of a nucleobase.
20. The kit of claim 15 , wherein the at least one mRNA is chemically modified.
21. The composition of claim 16 , wherein the at least one mRNA is chemically modified.