Composition for treating prostate cancer (PCa)
The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably an mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal wherein the antigens are selected from the group consisting of PSA (Prostate-Specific Antigen), PSMA (Prostate-Specific Membrane Antigen), PSCA (Prostate Stem Cell Antigen), and STEAP (Six Transmembrane Epithelial Antigen of the Prostate). The invention furthermore relates to a vaccine comprising an active (immunostimulatory) composition, and to the use of the active (immunostimulatory) composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of prostate cancer (PCa), preferably of neoadjuvant and/or hormone-refractory prostate cancers, and diseases or disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the active (immunostimulatory) composition and/or the vaccine.
1. An isolated mRNA comprising a Prostate Specific Membrane Antigen (PSMA) polypeptide coding sequence at least 80% identical to an mRNA encoded by the sequence of SEQ ID NO: 6, wherein the polypeptide coding sequence encodes the PSMA polypeptide sequence encoded by the sequence of SEQ ID NO: 6.
2. The isolated mRNA of claim 1 , wherein the polypeptide coding sequence is at least 85% identical to an mRNA encoded by the sequence of SEQ ID NO: 6.
3. The isolated mRNA of claim 2 , wherein the polypeptide coding sequence is at least 90% identical to an mRNA encoded by the sequence of SEQ ID NO: 6.
4. The isolated mRNA of claim 3 , wherein the polypeptide coding sequence is at least 95% identical to an mRNA encoded by the sequence of SEQ ID NO: 6.
5. The isolated mRNA of claim 4 , wherein the polypeptide coding sequence is at least 97% identical to an mRNA encoded by the sequence of SEQ ID NO: 6.
6. The isolated mRNA of claim 5 , wherein the polypeptide coding sequence is 100% identical to an mRNA encoded by the sequence of SEQ ID NO: 6.
7. The isolated mRNA of claim 1 , wherein the mRNA is complexed with as least one cationic or polycationic compound.
8. The isolated mRNA of claim 7 , wherein the cationic or polycationic compound is chosen from the group consisting of cationic lipids, cationic polysaccharides, cationic or polycationic peptides or proteins, or polycationic polymers.
9. The isolated mRNA of claim 8 , wherein the mRNA is complexed with protamine.
10. The isolated mRNA of claim 1 , wherein the mRNA comprises a 5′ cap structure.
11. The isolated mRNA of claim 1 , wherein the mRNA additionally comprises a poly-A tail of 10 to 200 adenosine nucleotides.
12. The isolated mRNA of claim 1 , wherein the mRNA additionally comprises a poly-C tail of 10 to 200 cytosine nucleotides.
13. The isolated mRNA of claim 1 , wherein the mRNA further comprises a 5′ and/or a 3′ untranslated region (UTR).
14. The isolated mRNA of claim 1 , wherein the mRNA comprises at least one nucleotide that is substituted with a nucleotide analog chosen from the group consisting of 5-methylcytidine and pseudouridine.
15. A method of treating a subject having prostate cancer comprising administering an effective amount an mRNA according to claim 1 to the subject.