초록 ▼

The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumor, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutic

The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumor, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutical composition. The pharmaceutical composition according to the invention is used in particular for therapy and/or prophylaxis against cancer.

대표청구항 ▼

1. A method of stimulating an antitumor immune response in a subject comprising administering an effective amount of a cell-free composition comprising mRNA encoding an PSA antigen to a subject in need thereof, thereby stimulating a T-cell mediated cytotoxic anticancer immune response in the subject

1. A method of stimulating an antitumor immune response in a subject comprising administering an effective amount of a cell-free composition comprising mRNA encoding an PSA antigen to a subject in need thereof, thereby stimulating a T-cell mediated cytotoxic anticancer immune response in the subject. 2. The method of claim 1, wherein the subject has a cancer. 3. The method of claim 2, wherein the cancer is a prostate cancer. 4. The method of claim 1, wherein the composition comprises mRNA encoding at least 2, 3, 4 or 5 different tumor antigens. 5. The method of claim 1, wherein the method further comprises administering at least 2, 3, 4 or 5 different cell-free compositions comprising mRNA encoding different tumor antigens to the subject. 6. The method of claim 1, wherein the mRNA is complexed with at least one cationic or polycationic agent. 7. The method of claim 6, wherein the cationic or polycationic agent is chosen from the group consisting of protamine, poly-L-lysine, poly-L-arginine and histones. 8. The method of claim 7, wherein the mRNA is complexed with protamine. 9. The method of claim 1, further comprising administering one or more adjuvant(s) to the subject. 10. The method of claim 9, wherein the adjuvant is chosen from the group consisting of lipopolysaccharide, TNF-α, CD40 ligand, GP96, oligonucleotides with a CpG motif, aluminum hydroxide, Freund's adjuvant, a lipopeptide and a cytokine. 11. The method of claim 10, wherein the cytokine is GM-CSF. 12. The method of claim 1, wherein the mRNA encoding the antigen has a different nucleic acid sequence compared with the wild-type mRNA encoding the antigen. 13. The method of claim 1, wherein the mRNA comprises a 5′ cap structure, at least one IRES and/or a poly(A+) tail of at least 25 nucleotides. 14. The method of claim 13, wherein the mRNA comprises a 5′ cap structure and a poly(A+) tail of at least 25 nucleotides. 15. The method of claim 1, wherein the mRNA comprises at least one 5′-stabilizing sequence and/or at least one 3′-stabilizing sequence. 16. The method of claim 15, wherein the 5′- and/or the 3′-stabilizing sequence(s) is/are chosen from the group consisting of untranslated sequences (UTR) of the β-globin gene and a stabilizing sequence of the general formula (C/U)CCANxCCC(U/A)PyxUC(C/U)CC. 17. The method of claim 1, wherein the mRNA comprises at least one analog of naturally occurring nucleotide selected from the group consisting of phoshorothioates, phosphoroamidates, peptide nucleotides, methylphosphates, 7-deazaguanosine, 5-methylcytosine and inosine. 18. The method of claim 1, wherein the cell-free composition comprising mRNA is administered by injection of an aqueous solution comprising the mRNA. 19. The method of claim 1, wherein the cell-free composition comprising mRNA is administered intradermally. 20. The method of claim 1, wherein the cell-free composition comprising mRNA is administered two or more times.