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 comprising administering to the subject an effective amount of:
(i) an immunogenic composition comprising at least one RNA encoding at least one antigen; and
(ii) an immune checkpoint inhibitor.
2 . The method of claim 1 , wherein the immune checkpoint inhibitor comprises a CTLA-4 pathway inhibitor or a PD-1 pathway inhibitor
3 . The method of claim 2 , wherein the CTLA-4 pathway inhibitor comprises an antibody directed against the CTLA-4 receptor.
4 . The method of claim 3 , wherein the subject has a cancer and the at least one RNA is a mRNA encoding a tumor antigen.
5 . The method of claim 2 , wherein the PD-1 pathway inhibitor comprises an inhibitor directed against PD-1.
6 . The method of claim 2 , wherein the PD-1 pathway inhibitor comprises an inhibitor directed against PD-L1 or PD-L2.
7 . The method of claim 1 , wherein the immune checkpoint inhibitor is administered after said immunogenic composition.
8 . The method of claim 1 , wherein the immune checkpoint inhibitor is comprises an antibody, a nucleic acid encoding an antibody or an siRNA.
9 . The method of claim 8 , wherein the immune checkpoint inhibitor is an antibody, or a nucleic-acid encoded antibody.
10 . The method of claim 1 , wherein the at least one RNA encodes an infectious disease antigen.
11 . The method of claim 1 , wherein the at least one RNA encodes a cancer or tumor cell antigen.
12 . The method of claim 1 , wherein the at least one RNA is an mRNA.
13 . The method of claim 1 , wherein the RNA is a codon optimized RNA.
14 . The method of claim 1 , wherein the at least one RNA comprises an increased G/C content relative to a wild type RNA encoding the antigen.
15 . The method of claim 1 , wherein the at least one RNA is complexed with a carrier.
16 . The method of claim 15 , wherein the carrier is a cationic, polycationic or polymeric carrier.
17 . The method of claim 16 , wherein the carrier comprises protamine.
18 . The method of claim 1 , wherein the subject has a cancer or tumor disease.
19 . A kit of parts comprising:
(i) an immunogenic composition comprising at least one RNA encoding at least one antigen; and
(ii) a composition comprising an immune checkpoint inhibitor.
20 . A pharmaceutical composition comprising an effective amount of: (i) at least one RNA encoding at least one antigen and (ii) an immune checkpoint inhibitor.