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 cancer in a patient in need thereof, the method comprising administering to the patient a pharmaceutically effective amount of a composition comprising an mRNA encoding IL-12, IL-18, IL-23 or OX4OL.
2 . The method of claim 1 , wherein administering comprises intratumoral application of the composition.
3 . The method of claim 2 , wherein intratumoral application of the composition comprises injection of the composition into the cancerous tissue.
4 . The method of claim 1 , further comprising the administration of at least a second anticancer therapy.
5 . The method of claim 4 , 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.
6 . The method of claim 5 , 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.
7 . The method of claim 5 , 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.
8 . The method of claim 7 , wherein the antagonistic antibody is directed against PD-1, PD-L1, or CTLA-4.
9 . The method of claim 7 , wherein the decoy receptor is a soluble PD-1 receptor.
10 . The method of claim 7 , wherein the checkpoint modulator comprising a mRNA encoding an agonistic antibody, an antagonistic antibody, a dominant negative receptor, a decoy receptor, or a ligand.
11 . 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.
12 . The method of claim 1 , wherein the mRNA comprises a 5′-UTR element and/or a 3′-UTR element.
13 . The method of claim 12 , wherein the mRNA comprises at least one histone stem-loop.
14 . The method of claim 12 , wherein the mRNA comprises a 5′-CAP structure, a poly(A) sequence, and/or a poly(C) sequence.
15 . The method of claim 1 , wherein the mRNA is complexed with one or more cationic or polycationic compound selected from the group consisting of cationic or polycationic polymers, cationic or polycationic peptides, or cationic or polycationic proteins, cationic or polycationic polysaccharides, and cationic or polycationic lipids.
16 . The method of claim 15 , wherein the cationic or polycationic protein is protamine.
17 . The method of claim 15 , wherein the N/P ratio of the mRNA to the one or more cationic or polycationic compound is in the range of about 0.1 to about 10.
18 . The method of claim 1 , wherein the mRNA is complexed with one or more lipids, thereby forming liposomes, lipid nanoparticles and/or lipoplexes.
19 . The method of claim 1 , wherein the cancer comprises are 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 bladder, uterus cancer or cervical cancer.