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 for treating a subject having cancer comprising administering (a) a composition comprising non-coding immunostimulating RNA (isRNA) of 5 to 1,000 bases in length to the subject by intratumoral injection, wherein the immunostimulating RNA is complexed with one or more cationic or polycationic compounds, and (b) an immune checkpoint modulator selected from a PD-1 inhibitor and a PD-L1 inhibitor.
2. The method of claim 1 , wherein the immunostimulating RNA comprises a sequence at least 90% identical to SEQ ID NO: 5, 394 or 10072.
3. The method of claim 1 , wherein the one or more cationic or polycationic compounds comprise polymers, peptides, polysaccharides, and/or lipids.
4. The method of claim 1 , wherein the cationic or polycationic compound is a polymeric carrier.
5. The method of claim 4 , wherein the polymeric carrier comprises disulfide-crosslinked cationic peptides.
6. The method of claim 4 , wherein the polymeric carrier comprises a cationic peptide CR 12 C and/or CR 12 .
7. The method of claim 1 , wherein the immunostimulating RNA comprises a sequence at least 90% identical to SEQ ID NO: 5 and the polymeric carrier comprises a cationic peptides comprising the sequence CR 12 C, said cationic peptides comprising crosslinks by C-C disulfide bonds.
8. The method of claim 1 , wherein the composition further comprises a mRNA encoding a cytokine.
9. The method of claim 8 , wherein the mRNA encoding a cytokine comprises a 5′-UTR element, a 3′-UTR element, a histone stem-loop, a 5′-CAP structure, a poly(A) sequence, and/or a poly(C) sequence.
10. The method of claim 1 , further comprising administering a cytokine.
11. The method of claim 10 , wherein the cytokine comprises IL-12.
12. The method of claim 10 , wherein the cytokine comprises a mRNA encoding IL-12.
13. The method of claim 12 , wherein the mRNA encoding IL-12 is administered via intratumoral injection.
14. The method of claim 1 , wherein the immune checkpoint modulator is a PD-L1 inhibitor.
15. The method of claim 1 , further comprising administering CD40L or an mRNA encoding CD40L to the subject.
16. The method of claim 14 , wherein the immune checkpoint modulator is an antibody directed against PD-L1.