Cancer vaccines targeting lemd1 and uses thereof

Abstract

Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a mutated consensus LEMD1 antigen. Vectors, compositions, and vaccines comprising one or more nucleic acid sequences that encode a mutated consensus LEMD1 antigen are disclosed. Methods of treating a subject with a LEMD1-expressing tumor and methods of preventing a LEMD1-expressing tumor are disclosed. Mutated consensus LEMD1 antigen is disclosed.

What is claimed is: 
     
         1 . A nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 (a) a nucleic acid sequence that encodes amino acid residues 19 to 198 of SEQ ID NO: 2;   (b) a nucleic acid sequence that encodes amino acid residues 19 to 84 of SEQ ID NO: 4;   (c) a nucleic acid sequence that encodes amino acid residues 19 to 198 and 206 to 271 of SEQ ID NO: 6;   (d) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein comprising amino acid residues 19 to 198 of SEQ ID NO: 2;   (e) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein comprising amino acid residues 19 to 84 of SEQ ID NO: 4;   (f) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein comprising amino acid residues 19 to 198 and 206 to 271 of SEQ ID NO: 6;   (g) a nucleic acid sequence that encodes a protein that is greater than 96% identical to amino acid residues 19 to 198 of SEQ ID NO: 2;   (h) a nucleic acid sequence that encodes a protein that is greater than 96% identical to amino acid residues 19 to 84 of SEQ ID NO: 4;   (i) a nucleic acid sequence that encodes a protein that is at least 95% identical to amino acid residues 19 to 198 and 206 to 271 of SEQ ID NO: 6;   (j) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein that is greater than 95.6% identical to amino acid residues 19 to 198 of SEQ ID NO: 2;   (k) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein that is greater than 95.5% identical to amino acid residues 19 to 84 of SEQ ID NO: 4; and   (l) a nucleic acid sequence that encodes a fragment comprising at least 90% of an entire length of a protein that is at least 95% identical to amino acid residues 19 to 198 and 206 to 271 of SEQ ID NO: 6.   
     
     
         2 . A protein comprising the amino acid sequence selected from the group consisting of:
 (a) amino acid residues 19 to 198 of SEQ ID NO: 2;   (b) amino acid residues 19 to 84 of SEQ ID NO: 4;   (c) amino acid residues 19 to 198 and 206 to 271 of SEQ ID NO: 6;   (d) a fragment comprising at least 90% of an entire length of amino acid residues 19 to 198 of SEQ ID NO: 2, wherein the fragment comprises at least one alanine amino acid residue at a position corresponding to position 37, 42, or 51 of SEQ ID NO: 2;   (e) a fragment comprising at least 90% of an entire length of amino acid residues 19 to 84 of SEQ ID NO: 4, wherein the fragment comprises at least one alanine amino acid residue at a position corresponding to position 37 or 42 of SEQ ID NO: 4;   (f) a fragment comprising at least 90% of an entire length of amino acid residues 19 to 198 and 206 to 271 SEQ ID NO: 6, wherein the fragment comprises at least one alanine amino acid residue at a position corresponding to position 37, 42, 51, 224, or 229 of SEQ ID NO: 6;   (g) an amino acid sequence that is greater than 95.6% identical to amino acid residues 19 to 198 of SEQ ID NO: 2, wherein the amino acid sequence comprises at least one alanine amino acid residue at a position corresponding to position 37, 42, or 51 of SEQ ID NO: 2;   (h) an amino acid sequence that is greater than 95.5% identical to amino acid residues 19 to 84 of SEQ ID NO: 4, wherein the amino acid sequence comprises at least one alanine amino acid residue at a position corresponding to position 37 or 42 of SEQ ID NO: 4;   (i) an amino acid sequence that is at least 95% identical to amino acid residues 19 to 198 and 206 to 271 of SEQ ID NO: 6, wherein the amino acid sequence comprises at least one alanine amino acid residue at a position corresponding to position 37, 42, 51, 224, or 229 of SEQ ID NO: 6;   (j) a fragment comprising at least 90% of an entire length of an amino acid sequence that is greater than 95.6% identical to amino acid sequences 19 to 198 of SEQ ID NO: 2, wherein the fragment comprises at least one alanine amino acid residue at a position corresponding to position 37, 42, or 51 of SEQ ID NO: 2;   (k) a fragment comprising at least 90% of an entire length of an amino acid sequence that is greater than 95.5% identical to amino acid sequences 19 to 84 of SEQ ID NO: 4, wherein the fragment comprises at least one alanine amino acid residue at a position corresponding to position 37 or 42 of SEQ ID NO: 4;   (l) a fragment comprising at least 90% of an entire length of an amino acid sequence that is at least 95% identical to amino acid sequences 19 to 198 and 206 and 271 of SEQ ID NO: 6, wherein the fragment comprises at least one alanine amino acid residue at a position corresponding to position 37, 42, 51, 224, or 229 of SEQ ID NO: 6;   (m) an amino acid sequence set forth in SEQ ID NO: 2;   (n) an amino acid sequence set forth in SEQ ID NO: 4, and   (o) an amino acid sequence set forth in SEQ ID NO: 6.   
     
     
         3 . A vaccine comprising a nucleic acid encoding an antigen, wherein the antigen comprises the protein of  claim 2 . 
     
     
         4 . The vaccine of  claim 3 , wherein the antigen is encoded by a nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
 (a) nucleotides 55 to 600 of SEQ ID NO: 1;   (b) nucleotides 55 to 258 of SEQ ID NO: 3;   (c) nucleotides 55 to 594 and 616 to 819 of SEQ ID NO: 5;   (d) a fragment comprising at least 90% of an entire length of a nucleic acid molecule comprising nucleotides 55 to 600 of SEQ ID NO: 1;   (e) a fragment comprising at least 90% of an entire length of a nucleic acid molecule comprising nucleotides 55 to 258 of SEQ ID NO: 3;   (f) a fragment comprising at least 90% of an entire length of a nucleic acid molecule comprising nucleotides 55 to 594 and 616 to 819 of SEQ ID NO: 5;   (g) a fragment that is at least 95% identical to nucleotides 55 to 600 of SEQ ID NO: 1;   (h) a fragment that is at least 95% identical to nucleotides 55 to 258 of SEQ ID NO: 3;   (i) a fragment that is at least 95% identical to nucleotides 55 to 594 and 616 to 819 of SEQ ID NO: 5;   (j) a fragment comprising at least 90% of an entire length of a nucleic acid sequence that is at least 95% identical to nucleotides 55 to 600 of SEQ ID NO: 1;   (k) a fragment comprising at least 90% of an entire length of a nucleic acid sequence that is at least 95% identical to nucleotides 55 to 258 of SEQ ID NO: 3;   (l) a fragment comprising at least 90% of an entire length of a nucleic acid sequence that is at least 95% identical to nucleotides 55 to 594 and 616 to 819 of SEQ ID NO: 1;   (m) nucleic acid sequence set forth in SEQ ID NO: 1;   (n) nucleic acid sequence set forth in SEQ ID NO: 3; and   (o) nucleic acid sequence set forth in SEQ ID NO: 5.   
     
     
         5 . The vaccine of  claim 4 , wherein the nucleic acid molecule comprises an expression vector. 
     
     
         6 . The vaccine of  claim 4 , comprising a pharmaceutically acceptable excipient. 
     
     
         7 . The vaccine of  claim 4 , comprising an adjuvant. 
     
     
         8 . The vaccine of  claim 7 , wherein the adjuvant is IL-12, IL-15, IL-28, or RANTES. 
     
     
         9 . A vaccine comprising a nucleic acid molecule or a peptide, wherein the nucleic acid molecule or the peptide comprises
 (a) a nucleic acid sequence having at least about 95% identity over an entire length of the nucleic acid sequence set forth in SEQ ID NO: 1, 3, or 5;   (b) a nucleic acid molecule encoding a peptide comprising an amino acid sequence having at least about 95.6%, 95.5%, or 95% identity over an entire length of the amino acid sequence set forth in SEQ ID NO: 2, 4, or 6, respectively;   (c) a peptide comprising an amino acid sequence having at least about 95.6%, 95.5%, or 95% identity over an entire length of the amino acid sequence set forth in SEQ ID NO: 2, 4, or 6, respectively; or   (d) a peptide comprising the amino acid sequence set forth in SEQ ID NO: 2, 4, or 6.   
     
     
         10 . The vaccine of  claim 9 , wherein the nucleic acid molecule comprises an expression vector. 
     
     
         11 . The vaccine of  claim 9 , comprising a pharmaceutically acceptable excipient. 
     
     
         12 . The vaccine of  claim 9 , comprising an adjuvant. 
     
     
         13 . The vaccine of  claim 12 , wherein the adjuvant is IL-12, IL-15, IL-28, or RANTES. 
     
     
         14 . A method of treating a subject having a LEMD1-expressing cancerous cell comprising administering a therapeutically effective amount of the vaccine of  claim 3  to the subject. 
     
     
         15 . The method of  claim 14 , wherein administration includes an electroporation step. 
     
     
         16 . The method of  claim 14 , wherein administration occurs at one or more sites on the subject. 
     
     
         17 . A method of treating a subject having a LEMD1-expressing cancerous cell comprising administering a therapeutically effective amount of the vaccine of  claim 9  to the subject. 
     
     
         18 . The method of  claim 17 , wherein administration includes an electroporation step. 
     
     
         19 . The method of  claim 17 , wherein administration occurs at one or more sites on the subject. 
     
     
         20 . A method of vaccinating a subject against a LEMD1-expressing cancerous cell comprising administering an amount of the vaccine of  claim 3  effective to induce a humoral immune response to the subject. 
     
     
         21 . The method of  claim 20 , wherein administration includes an electroporation step. 
     
     
         22 . The method of  claim 20 , wherein administration occurs at one or more sites on the subject. 
     
     
         23 . A method of vaccinating a subject against a LEMD1-expressing cancerous cell comprising administering an amount of the vaccine of  claim 9  effective to induce a humoral immune response to the subject. 
     
     
         24 . The method of  claim 23 , wherein administration includes an electroporation step. 
     
     
         25 . The method of  claim 24 , wherein administration occurs at one or more sites on the subject.