Combination of vaccination and OX40 agonists
The present invention relates to a vaccine/agonist 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 OX40 agonist. The present invention furthermore relates to a pharmaceutical composition and a kit of parts comprising the components of such a vaccine/agonist combination. Additionally the present invention relates to medical use of such a vaccine/agonist combination, the pharmaceutical composition and the kit of parts comprising such a vaccine/agonist 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 an OX40 agonist.
1. A method of treatment comprising administering to a subject in need thereof a therapeutically effective amount of:
(i) at least one RNA comprising at least one open reading frame (ORF) coding for at least one antigen and
(ii) a composition comprising an agonistic antibody or an antigen binding fragment thereof, or a nucleic acid encoding said agonistic antibody or antigen binding fragment thereof, wherein said antibody or antigen binding from fragment thereof is directed against OX40.
2. The method of claim 1 , wherein the agonistic antibody directed against OX40 is monoclonal antibody 9B12.
3. The method of claim 1 , wherein the at least one RNA is an isolated RNA.
4. The method of claim 1 , wherein the at least one RNA is a stabilized RNA.
5. The method of claim 1 , wherein the at least one RNA is at least partially G/C modified, wherein the G/C content of the at least one open reading frame of the at least one RNA is increased compared to the wild type open reading frame.
6. The method of claim 1 , wherein the at least one RNA comprises a codon-optimized region, wherein the at least one open reading frame of the at least one RNA is codon-optimized.
7. The method of claim 1 , wherein the at least one RNA is an mRNA.
8. The method of claim 1 , wherein the at least one RNA is complexed with a carrier.
9. The method of claim 1 , wherein the agonistic antibody or an antigen binding fragment thereof, or a nucleic acid encoding said agonistic antibody or antigen binding fragment thereof is administered prior to the at least one RNA.
10. The method of claim 1 , wherein the agonistic antibody or an antigen binding fragment thereof, or a nucleic acid encoding said agonistic antibody or antigen binding fragment thereof is administered after the at least one RNA.
11. The method of claim 1 , wherein the agonistic antibody or an antigen binding fragment thereof, or a nucleic acid encoding said agonistic antibody or antigen binding fragment thereof is administered essentially simultaneously with the at least one RNA.
12. The method of claim 8 , wherein the at least one RNA is complexed with a cationic carrier.
13. The method of claim 12 , wherein the cationic carrier is a lipid.