RNA containing composition for treatment of tumor diseases
The present invention relates to RNA containing compositions for use in the treatment or prophylaxis of tumor and/or cancer diseases, to a pharmaceutical composition, to a kit and to uses of the RNA containing compositions for the treatment or prophylaxis of tumor and/or cancer diseases.
1. A method of treating solid tumor in a patient in need thereof, the method comprising administering intratumorally to the tumor in the patient a pharmaceutically effective amount of a composition comprising an mRNA encoding IL-23 and having at least about 90% identity to wild-type mature human IL-23, wherein the mRNA encoding IL-23 is complexed with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.
2. The method of claim 1 , further comprising the administration of at least a second anticancer therapy.
3. The method of claim 2 , wherein the second anticancer therapy is a chemotherapy, a hormone therapy, an immunotherapy, a checkpoint modulator therapy, a cytokine therapy, a radiation therapy, and/or a surgery.
4. The method of claim 3 , wherein the checkpoint modulator therapy is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a LAG3 inhibitor, a TIM3 inhibitor, an OX-40 stimulator, a 4-1BB stimulator, a CD40L stimulator, a CD28 stimulator, and a GITR stimulator.
5. The method of claim 3 , wherein the checkpoint modulator therapy is selected from the group consisting of an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, and a ligand.
6. The method of claim 5 , wherein the antagonistic antibody is directed against PD-1, PD-L1, or CTLA-4.
7. The method of claim 5 , wherein the decoy receptor is a soluble PD-1 receptor.
8. The method of claim 5 , wherein the checkpoint modulator comprising a mRNA encoding an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, or a ligand.
9. The method of claim 1 , wherein the G/C content of the coding region of the mRNA is increased compared with the G/C content of the coding region of the wild type mRNA, and wherein the coded amino acid sequence of said G/C-enriched mRNA is not modified compared with the encoded amino acid sequence of the wild type mRNA.
10. The method of claim 1 , wherein the mRNA comprises a 5′-UTR element and/or a 3′-UTR element.
11. The method of claim 10 , wherein the mRNA comprises at least one histone stem-loop.
12. The method of claim 10 , wherein the mRNA comprises a 5′-CAP structure, a poly(A) sequence, and/or a poly(C) sequence.
13. The method of claim 1 , wherein the lipid is a cationic or polycationic lipid.
14. The method of claim 1 , wherein the cancer is prostate cancer, lung cancer, breast cancer, brain cancer, head and neck cancer, thyroid cancer, colon cancer, stomach cancer, liver cancer, pancreas cancer, ovary cancer, skin cancer, urinary cancer, bladder cancer, uterine cancer, lymphoma or cervical cancer.
15. The method of claim 1 , further comprising administering at least a second mRNA encoding a cytokine.
16. The method of claim 15 , comprising administering at least a second mRNA encoding IL-18.
17. The method of claim 1 , wherein the mRNA encoding IL-23 comprises a 5′-CAP structure and a poly(A) sequence, and wherein the composition is administered by injection into tumor tissue.
18. The method of claim 17 , further comprising administering at least a second mRNA encoding IL-18.
19. The method of claim 2 , wherein the second cancer therapy is administering at least a second mRNA encoding OX40L.