Cancer Vaccines Targeting PRAME and Uses Thereof

Abstract

Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a mutated consensus PRAME antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a mutated consensus PRAME antigen are disclosed. Methods of treating a subject with a PRAME-expressing tumor and methods of preventing a PRAME-expressing tumor are disclosed. Mutated consensus PRAME antigen is disclosed.

What is claimed is: 
     
         1 . A nucleic acid molecule comprising:
 a nucleic acid sequence as set forth in SEQ ID NO: 1;   a nucleic acid sequence as set forth in nucleotides 55 to 1584 of SEQ ID NO: 1;   a nucleic acid sequence that encodes the amino acid sequence set forth in SEQ ID NO: 2; or   a nucleic acid sequence that encodes the amino acid sequence as set forth in amino acid residues 19 to 526 of SEQ ID NO: 2.   
     
     
         2 . A protein comprising one or more amino acid sequences selected from the group consisting of:
 (a) an amino acid sequence as set forth in SEQ ID NO: 2;   (b) an amino acid sequence that is at least 96% identical to SEQ ID NO: 2, wherein the amino acid sequence comprises a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) an amino acid sequence as set forth in amino acid residues 19 to 526 of SEQ ID NO: 2; and   (d) an amino acid sequence that is at least 96% identical to amino acids 19 to 526 of SEQ ID NO: 2, wherein the amino acid sequence comprises a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         3 . A vaccine comprising a nucleic acid molecule encoding the protein of  claim 2 . 
     
     
         4 . The vaccine of  claim 3 , wherein the nucleic acid molecule comprises one or more nucleic acid sequences selected from the group consisting of:
 (a) a nucleic acid sequence as set forth in SEQ ID NO: 1;   (b) a nucleic acid sequence that is at least 96% identical to SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) a nucleic acid sequence as set forth in nucleotides 55 to 1584 of SEQ ID NO: 1; and   (d) a nucleic acid sequence that is at least 96% identical to nucleotides 55 to 1584 of SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         5 . The vaccine of  claim 3  further comprising a pharmaceutically acceptable excipient. 
     
     
         6 . The vaccine of any  claim 3  further comprising an adjuvant. 
     
     
         7 . The vaccine of  claim 6 , wherein the adjuvant is IL-12, IL-15, IL-28, or RANTES. 
     
     
         8 . A method of treating a subject having a cell characterized by aberrant PRAME expression comprising administering to the subject a therapeutically effective amount of a vaccine comprising a nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 (a) SEQ ID NO: 1;   (b) a nucleic acid sequence that is at least 96% identical to SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) a nucleic acid sequence comprising nucleotides 55 to 1584 of SEQ ID NO: 1; and   (d) a nucleic acid sequence that is at least 96% identical to nucleotides 55 to 1584 of SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         9 . A method of treating a subject having a cell characterized by aberrant PRAME expression comprising administering to the subject a therapeutically effective amount of a vaccine comprising a nucleic acid molecule encoding an antigen, wherein the antigen is a protein comprising one or more amino acid sequences selected from the group consisting of:
 (a) an amino acid sequence as set forth in SEQ ID NO: 2;   (b) an amino acid sequence that is at least 96% identical to SEQ ID NO: 2, wherein the amino acid sequence comprises a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) an amino acid sequence as set forth in amino acid residues 19 to 526 of SEQ ID NO: 2; and   (d) an amino acid sequence that is at least 96% identical to amino acids 19 to 526 of SEQ ID NO: 2, wherein the amino acid sequence comprises a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         10 . A method of treating cancer in a subject, the method comprising administering to the subject a therapeutically effective amount of a vaccine comprising a nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 (a) SEQ ID NO: 1;   (b) a nucleic acid sequence that is at least 96% identical to SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) a nucleic acid sequence comprising nucleotides 55 to 1584 of SEQ ID NO: 1; and   (d) a nucleic acid sequence that is at least 96% identical to nucleotides 55 to 1584 of SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         11 . The method of  claim 10  wherein the cancer is ovarian cancer. 
     
     
         12 . The method of  claim 11 , wherein the cancer is epithelial ovarian cancer. 
     
     
         13 . The method of  11 , wherein the cancer is serous ovarian cancer. 
     
     
         14 . A method of vaccinating a subject against cells characterized by aberrant PRAME expression comprising administering an amount of a vaccine effective to elicit an immune response, wherein the vaccine comprises a nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 (a) SEQ ID NO: 1;   (b) a nucleic acid sequence that is at least 96% identical to SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) a nucleic acid sequence comprising nucleotides 55 to 1584 of SEQ ID NO: 1; and   (d) a nucleic acid sequence that is at least 96% identical to nucleotides 55 to 1584 of SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         15 . A method of vaccinating a subject against cells characterized by aberrant PRAME expression comprising administering an amount of a vaccine effective to elicit an immune response, wherein the vaccine comprises a nucleic acid molecule encoding an antigen, wherein the antigen is a protein comprising one or more amino acid sequences selected from the group consisting of:
 (a) an amino acid sequence as set forth in SEQ ID NO: 2;   (b) an amino acid sequence that is at least 96% identical to SEQ ID NO: 2, wherein the amino acid sequence comprises a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) an amino acid sequence as set forth in amino acid residues 19 to 526 of SEQ ID NO: 2; and   (d) an amino acid sequence that is at least 96% identical to amino acids 19 to 526 of SEQ ID NO: 2, wherein the amino acid sequence comprises a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         16 . A method of eliciting an immune response in a subject comprising administering to the subject a therapeutically effective amount of a vaccine comprising a nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 (a) SEQ ID NO: 1;   (b) a nucleic acid sequence that is at least 96% identical to SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2;   (c) a nucleic acid sequence comprising nucleotides 55 to 1584 of SEQ ID NO: 1; and   (d) a nucleic acid sequence that is at least 96% identical to nucleotides 55 to 1584 of SEQ ID NO: 1, wherein the nucleic acid encodes a valine at amino acid position 487 and a valine at amino acid position 488 relative to SEQ ID NO: 2.   
     
     
         17 . The method of  claim 16 , wherein the elicited immune response is a cellular response, a humoral immune response, or both a cellular immune response and a humoral immune response. 
     
     
         18 . The method of  claim 16 , wherein the cellular immune response comprises induction or secretion of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), or both. 
     
     
         19 . The method of  claim 16 , wherein the elicited immune response comprises inhibition of one or more immune suppression factors that promote growth of a cell, tumor, or cancer expressing a PRAME antigen. 
     
     
         20 . The method of  claim 16 , wherein the administering comprises electroporation. 
     
     
         21 . The method of  claim 16 , wherein the vaccine is administered at one or more sites on the subject.