Composition for treating lung cancer, particularly of non-small lung cancers (nsclc)

Abstract

The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably a mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal. The invention furthermore relates to a vaccine comprising said active (immunostimulatory) composition, and to the use of said active (immunostimulatory) composition (for the preparation of a vaccine) and/or of the vaccine for eliciting an (adaptive) immune response for the treatment of lung cancer, particularly of non-small cell lung cancers (NSCLC), preferably selected from the three main sub-types squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma, or of disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the active (immunostimulatory) composition and/or the vaccine.

1 - 24 . (canceled) 
     
     
         25 . A kit comprising at least five different immunostimulatory compositions, wherein the at least five different immunostimulatory compositions are:
 (a) an immunostimulatory composition comprising an isolated NY-ESO-1 antigen coding RNA;   (b) an immunostimulatory composition comprising an isolated MAGE-C1 antigen coding RNA;   (c) an immunostimulatory composition comprising an isolated MAGE-C2 antigen coding RNA;   (d) an immunostimulatory composition comprising an isolated 5T4 antigen coding RNA; and   (e) an immunostimulatory composition comprising an isolated Survivin antigen coding RNA.   
     
     
         26 . The kit according to  claim 25 , wherein the at least five different immunostimulatory compositions are:
 (a) an immunostimulatory composition comprising an isolated NY-ESO-1 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 21 or being at least 80% identical to SEQ ID NO 21;   (b) an immunostimulatory composition comprising an isolated MAGE-C1 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 24 or being at least 80% identical to SEQ ID NO 24;   (c) an immunostimulatory composition comprising an isolated MAGE-C2 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 26 or being at least 80% identical to SEQ ID NO 26;   (d) an immunostimulatory composition comprising an isolated 5T4 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 4 or being at least 80% identical to SEQ ID NO 4; and   (e) an immunostimulatory composition comprising an isolated Survivin antigen coding RNA comprising an RNA sequence according to SEQ ID NO 19 or being at least 80% identical to SEQ ID NO 19.   
     
     
         27 . The kit according to  claim 25 , further comprising an immunostimulatory composition comprising an isolated MUC-1 antigen coding RNA. 
     
     
         28 . The kit according to  claim 26 , further comprising
 (f) an immunostimulatory composition comprising an isolated MUC-1 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 2 or being at least 80% identical to SEQ ID NO 2.   
     
     
         29 . The kit according to  claim 26 , wherein the at least five different immunostimulatory compositions are:
 (a) an immunostimulatory composition comprising an isolated NY-ESO-1 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 21 or a variant thereof;   (b) an immunostimulatory composition comprising an isolated MAGE-C1 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 24 or a variant thereof;   (c) an immunostimulatory composition comprising an isolated MAGE-C2 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 26 or a variant thereof;   (d) an immunostimulatory composition comprising an isolated 5T4 antigen coding RNA comprising an RNA sequence according to SEQ ID NO 4 or a variant thereof; and   (e) an immunostimulatory composition comprising an isolated Survivin antigen coding RNA comprising an RNA sequence according to SEQ ID NO 19 or a variant thereof;   wherein the variant of the antigen coding RNA has at least one nucleic acid exchanged according to the degeneration of the genetic code, without leading to an alteration of the respective amino acid sequence of the antigen.   
     
     
         30 . The kit according to  claim 25 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is mRNA. 
     
     
         31 . The kit according to  claim 25 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that is monocistronic RNA. 
     
     
         32 . The kit according to  claim 25 , wherein the antigen coding RNA of said at least five different immunostimulatory compositions is monocistronic RNA. 
     
     
         33 . The kit according to  claim 30 , wherein the mRNA comprises a G/C content of the antigen coding region that is increased compared to the G/C content of a wild-type RNA encoding the antigen. 
     
     
         34 . The kit according to  claim 30 , wherein the mRNA comprises a A/U content in the environment of the ribosome binding site that is increased compared with the A/U content of a wild-type RNA encoding the antigen. 
     
     
         35 . The kit according to  claim 30 , wherein the mRNA comprises a 5′ untranslated region (5′UTR) and/or 3′ untranslated region (3′UTR) that is modified compared to a wild-type RNA encoding the antigen. 
     
     
         36 . The kit according to  claim 30 , wherein the mRNA comprises a 5′ cap structure; a poly(A) tail; a poly(C) tail; and/or a globin 3′UTR. 
     
     
         37 . The kit according to  claim 25 , wherein at least one the RNAs is complexed with one or more polycations. 
     
     
         38 . The kit according to  claim 37 , wherein the polycation is protamine. 
     
     
         39 . The kit according to  claim 25 , wherein at least one of said at least five different immunostimulatory compositions comprises at least one adjuvant. 
     
     
         40 . The kit according to  claim 25 , wherein at least one of said at least five different immunostimulatory compositions comprises a pharmaceutically acceptable carrier. 
     
     
         41 . A method of treating lung cancer in a subject comprising administering an effective amount of said at least five different immunostimulatory compositions of a kit according to  claim 25  to the subject. 
     
     
         42 . The method according to  claim 41 , wherein the lung cancer is non-small-cell lung cancer (NSCLC). 
     
     
         43 . The kit of  claim 25 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that comprises a globin 3′ UTR. 
     
     
         44 . The kit according to  claim 25 , wherein each of said different immunostimulatory compositions comprises isolated mRNA complexed with protamine and wherein each of said different immunostimulatory compositions comprises mRNA comprising a 5′ cap structure, a poly(A) tail, a globin 3′ UTR, and a G/C content of the antigen coding region, which is increased compared to the G/C content of wild-type RNA encoding the antigen. 
     
     
         45 . The kit according to  claim 26 , wherein each of said different immunostimulatory compositions comprises isolated mRNA complexed with protamine and wherein each of said different immunostimulatory compositions-comprises mRNA comprising a 5′ cap structure, a poly(A) tail, a globin 3′ UTR, and a G/C content of the antigen coding region, which is increased compared to the G/C content of wild-type RNA encoding the antigen. 
     
     
         46 . The kit according to  claim 30 , wherein the mRNA comprises a 3′UTR that does not comprise an AU-rich sequence. 
     
     
         47 . The kit according to  claim 30 , wherein at least one of said at least five different immunostimulatory compositions comprises RNA that does not comprise the sequence GAACAAG. 
     
     
         48 . A method of treating lung cancer in a subject comprising administering an effective amount of said at least five different immunostimulatory compositions of a kit according to  claim 26  to the subject.