Therapeutic anticancer neoepitope vaccine

Abstract

The present invention relates to an anticancer vaccine comprising polynucleotides or polypeptides, methods of treatment of targeting module cancer wherein such an anticancer vaccine is used as well as methods for producing the vaccine. The vaccine comprises a polynucleotide comprising a nucleotide sequence encoding a targeting unit, a dimerization unit, a first linker and an antigenic unit, wherein said antigenic unit comprises n−1 antigenic subunits, each subunit comprising at least a part of a cancer neoepitope sequence and a second linker and said antigenic unit further comprising a final cancer neoepitope sequence, wherein n is an integer of from 3 to 50, or the vaccine comprises a polypeptide encoded by the polynucleotide or a dimeric protein consisting of two polypeptides encoded by the polynucleotide.

1 . A therapeutic anticancer neoepitope vaccine comprising an immunologically effective amount of
 a polynucleotide comprising a nucleotide sequence encoding
 a targeting unit 
 a dimerization unit 
 a first linker 
 an antigenic unit, wherein said antigenic unit comprises n−1 antigenic subunits, each subunit comprising at least a part of a cancer neoepitope sequence and a second linker and said antigenic unit further comprising a final cancer neoepitope sequence, wherein n is an integer of from 3 to 50. 
   or   a polypeptide encoded by the polynucleotide as defined in 1), or   a dimeric protein consisting of two polypeptides encoded by the polynucleotide as defined in 1).   
     
     
         2 . The vaccine according to  claim 1 , wherein the antigenic unit comprises one copy of each cancer neoepitope. 
     
     
         3 . The vaccine according to  claim 1 , wherein the antigenic unit comprises at least two copies of at least one neoepitope. 
     
     
         4 . The vaccine according to any of the preceding claims, wherein the cancer neoepitope sequence has a length of from 7 to 30 amino acids. 
     
     
         5 . The vaccine according to any of the preceding claims, wherein each cancer neoepitope sequence has identical length. 
     
     
         6 . The vaccine according to any of the preceding claims, wherein the cancer neoepitope is positioned essentially in the middle of the cancer neoepitope sequence. 
     
     
         7 . The vaccine according to any of the preceding claims, wherein the cancer neoepitope sequence is a subsequence of a cancer neoantigen. 
     
     
         8 . The vaccine according to any of the preceding claims, wherein the antigenic subunits are in the order of more antigenic to less antigenic from the first linker. 
     
     
         9 . The vaccine according to any of the preceding claims, wherein the most hydrophobic antigenic subunit(s) is(are) substantially the middle of the antigenic unit and the most hydrophilic antigenic subunit(s) is/are at the ends of the antigenic unit. 
     
     
         10 . The vaccine according to any of the preceding claims, wherein the second linker is a flexible linker. 
     
     
         11 . The vaccine according to any of the preceding claims, wherein the second linker is identical in all antigenic subunits. 
     
     
         12 . The vaccine according to any of the preceding claims, wherein the second linker is a Serine-Glycine linker. 
     
     
         13 . The vaccine according to any of the preceding claims, wherein the length of the antigenic unit is from about 300 amino acids to about a 1000 amino acids. 
     
     
         14 . The vaccine according to any of the preceding claims, wherein the dimerization unit comprises an amino acid sequence having at least 80% sequence identity to the amino acid sequence 94-237 of SEQ ID NO:3. 
     
     
         15 . The vaccine according to any of the preceding claims, wherein the targeting unit has affinity for a chemokine receptor selected from CCR1, CCR3 and CCR5. 
     
     
         16 . The vaccine according to any of the preceding claims, wherein said targeting unit, dimerization unit and antigenic unit in said peptide are in the N-terminal to C-terminal order of targeting unit, dimerization unit and antigenic unit. 
     
     
         17 . Use of a vaccine as defined in any of the  claims 1 - 16  for treatment of cancer.