Personalized vaccine

Abstract

The present invention generally relates to a personalized cancer vaccine comprising a recombinant poxvirus encoding one or more neopeptide(s) or a composition comprising such a recombinant poxvirus and a pharmaceutically acceptable vehicle as well as the use of said personalized cancer vaccine for treating a cancerous subject in need thereof. A specific embodiment is directed to a method of providing such a vaccine or composition comprising an identification step comprising a) extracting the DNA from a tumor sample and a non-tumor sample, b) selecting target regions, c) sequencing said target regions from said extracted DNAs and d) identifying one or more tumor-specific mutation(s) by comparing the DNA sequences obtained from said tumor and non-tumor samples. Embodiments also include a method of treating cancer or preventing its relapse comprising administration of such a personalized cancer vaccine. The invention is of very special interest in the field of personalized immunotherapy.

1 - 41 . (canceled) 
     
     
         42 . A recombinant poxvirus comprising one or more heterologous nucleic acid sequence,
 wherein each heterologous nucleic acid sequence encodes a neopeptide fusion comprising 2 to 15 neopeptides,   wherein at least 60% of said 2 to 15 neopeptides comprise a missense or a frameshift mutation, and   wherein said neopeptide fusion has a negative hydrophobicity score and/or a hydropathy score equal or below 0.1.   
     
     
         43 . The recombinant poxvirus of  claim 42 , wherein said recombinant poxvirus belongs to the Orthopoxvirus genus or the parapoxvirus genus. 
     
     
         44 . The recombinant poxvirus of  claim 43 , wherein said recombinant poxvirus is a vaccinia virus or a pseudocowpoxvirus. 
     
     
         45 . The recombinant poxvirus of  claim 42 , wherein each of said 2 to 15 neopeptides comprises at least one tumor-specific mutation. 
     
     
         46 . The recombinant poxvirus of  claim 45 , wherein the neopeptide fusion is not present in the proteome of the non-tumor sample. 
     
     
         47 . The recombinant poxvirus of  claim 42 , wherein at least 60% of said neopeptides comprise a missense mutation. 
     
     
         48 . The recombinant poxvirus of  claim 42 , wherein said neopeptides comprising a missense mutation have a length from 18 to 29 residues and/or said neopeptides comprising a frameshift mutation have a length from 30 to 80 amino acid residues. 
     
     
         49 . The recombinant poxvirus of  claim 42 , wherein at least 80% of said neopeptides comprising a missense mutation carry the substituted amino acid in central position. 
     
     
         50 . The recombinant poxvirus of  claim 42 , wherein said neopeptide fusion does not contain a predicted transmembrane segment. 
     
     
         51 . The recombinant poxvirus of  claim 42 , wherein said neopeptide fusion has a negative hydrophobicity score. 
     
     
         52 . The recombinant poxvirus of  claim 42 , wherein the recombinant poxvirus comprises two or three heterologous nucleic acid sequences, wherein:
 each neopeptide fusion comprises 5 to 10 neopeptides;   each neopeptide fusion comprises linkers, preferably of 3 amino acid long, at the N-terminus of the first neopeptide, and between each neopeptide; and   each neopeptide fusion comprises a signal peptide at the N terminus of said fusion; and   each neopeptide fusion does not contain a predicted transmembrane segment.   
     
     
         53 . The recombinant poxvirus of  claim 42 , wherein said recombinant poxvirus comprises one to three heterologous nucleic acid sequences, wherein expression of each neopeptide fusion is under the transcriptional control of a vaccinia promoter selected from the group consisting of p11k7.5, pH5R, p7.5K, and pB2R. 
     
     
         54 . The recombinant poxvirus of  claim 42 , wherein said recombinant poxvirus further encodes one or more therapeutic genes. 
     
     
         55 . A composition comprising a therapeutically effective amount of said recombinant poxvirus of  claim 42  and a pharmaceutically acceptable vehicle. 
     
     
         56 . The composition of  claim 55 , wherein said therapeutically effective amount for individual doses comprises approximately 5×10 7  pfu to approximately 10 9  pfu. 
     
     
         57 . The composition of  claim 55 , wherein said composition is a personalized cancer vaccine. 
     
     
         58 . The recombinant poxvirus of  claim 44 , wherein said recombinant poxvirus is a Modified Vaccinia Ankara (MVA) virus. 
     
     
         59 . The recombinant poxvirus of  claim 54 , wherein the one or more therapeutic genes is a suicide gene and/or an immunostimulatory gene. 
     
     
         60 . A method of treating or preventing cancer in a subject in need thereof, comprising administering the recombinant poxvirus of  claim 42  to said subject. 
     
     
         61 . The method of  claim 60 , wherein the cancer is a solid tumor.