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 - 62 . (canceled)
63 . A pharmaceutical composition comprising a RNA complexed with one or more lipids, thereby forming lipid nanoparticles, said RNA comprising a 5′ cap, 5′ untranslated region (UTR), a coding sequence encoding a first cytokine, a 3′ UTR, and a poly-A sequence.
64 . A method of treating a subject having cancer comprising administering to the subject the pharmaceutical composition according to claim 63 , wherein the subject has a solid tumor and wherein said composition is administered by intratumoral injection.
65 . The method of claim 64 , wherein in the first cytokine is an interleukin.
66 . The method of claim 65 , wherein the first cytokine is IL-12.
67 . The method of claim 65 , wherein the first cytokine is IL-23.
68 . The method of claim 64 , wherein in the first cytokine is a member of the TNF family.
69 . The method of claim 68 , wherein in the first cytokine is OX40L.
70 . The method of claim 64 , wherein RNA is a replicon RNA.
71 . The method of claim 64 , wherein RNA is a mRNA having a poly-A sequence of 60 to 250 adenosine nucleotides.
72 . The method of claim 64 , wherein the composition further comprises a RNA encoding a second cytokine.
73 . The method of claim 72 , wherein the first cytokine is an interleukin and the second cytokine is a member of the TNF family.
74 . The method of claim 64 , further comprising administering at least a second anticancer therapy to the subject.
75 . The method of claim 74 , wherein the second therapy is a chemotherapy, an immunotherapy, a checkpoint modulator therapy, a radiation therapy, or a surgery.
76 . The method of claim 75 , 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 LAGS inhibitor, a TIM3 inhibitor, an OX-40 stimulator, a 4-1BB stimulator, a CD40L stimulator, a CD28 stimulator, and a GITR stimulator.
77 . The method of claim 75 , wherein the checkpoint modulator therapy is an antibody therapy.
78 . The method of claim 77 , wherein the antibody therapy comprises an antagonistic antibody directed against PD-1, PD-L1, or CTLA-4.
79 . The method of claim 64 , 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, or cervical cancer.
80 . The method of claim 64 , wherein the cancer is a metastatic cancer.