Disclosed herein are nucleic acid molecules comprising one or more nucleic acid sequences that encode a mutated WT1 antigen. Vectors, compositions and vaccines comprising one or more nucleic acid sequences that encode a mutated WT1 antigen are disclosed. Methods of treating an individual who has a WT1-expressing tumor and methods of preventing a WT1-expressing tumor are disclosed. Mutated WT1 antigen is disclosed.
1 . An isolated nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO: 1 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:1 without the leader sequence, a nucleic acid sequence that is at least 98% identical to SEQ ID NO: 1 over the entire length of SEQ ID NO: 1 without the leader sequence, a fragment comprising at least 90% of the entire length of a nucleic acid sequence that is at least 98% identical to SEQ ID NO: 1 over the entire length of SEQ ID NO:1 without the leader sequence, SEQ ID NO: 3 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:3 without the leader sequence, a nucleic acid sequence that is at least 98% identical to SEQ ID NO:3 over the entire length of SEQ ID NO:3 without the leader sequence, and a fragment comprising at least 90% of the entire length of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:3 over the entire length of SEQ ID NO:3 without the leader sequence.
2 . The isolated nucleic acid molecule of claim 1 , wherein the isolated nucleic molecule is incorporated into a plasmid or a viral vector.
3 . The isolated nucleic acid molecule of claim 1 , wherein the nucleic acid sequences encodes a protein or a fragment thereof comprising an amino acid sequence selected from the group consisting of: SEQ ID NO:2 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:2 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, SEQ ID NO:4 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:4 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence, and a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4 without the leader sequence.
4 . A composition comprising the isolated nucleic acid molecule of claim 1 .
5 . A vaccine comprising the isolated nucleic acid molecule of claim 1 .
6 . The vaccine of claim 5 , wherein the isolated nucleic acid molecule is incorporated into an expression vector.
7 . The vaccine of claim 5 , further comprising a pharmaceutically acceptable excipient.
8 . The vaccine of claim 5 , further comprising an adjuvant.
9 . The vaccine of claim 5 , further comprising an amino acid sequence selected from the group consisting of: SEQ ID NO:2 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:2 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, SEQ ID NO:4 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence, and a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence.
10 . The vaccine of claim 9 , wherein the one or more nucleic acids are incorporated into an expression vector.
11 . The vaccine of claim 9 , further comprising a pharmaceutically acceptable excipient.
12 . The vaccine of claim 9 , further comprising an adjuvant.
13 . A method of treating an individual who has a WT1-expressing tumor or preventing development of a WT1-expressing tumor in an individual comprising administering an amount of the vaccine of claim 5 effective to slow growth of, reduce, or eliminate WT1-expressing tumors.
14 . A method of treating an individual who has a WT1-expressing tumor or preventing development of a WT1-expressing tumor comprising administering an amount of the vaccine of claim 9 effective to slow growth of, reduce, or eliminate WT1-expressing tumors.
15 . A method of treating an individual who has a WT1-expressing tumor or preventing development of a WT1-expressing tumor comprising administering an amount of a vaccine effective to slow growth of, reduce, or eliminate WT1-expressing tumors, wherein the vaccine comprises a nucleic acid molecule comprising one or more nucleic acid sequences encoding a protein or a fragment thereof, wherein the protein comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:2 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO: 2 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, SEQ ID NO:4 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:4 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO: 4 without the leader sequence, and a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence.
16 . The method of claim 15 , wherein the protein comprises the amino acid sequence as set forth in SEQ ID NO:2 without the leader sequence.
17 . A method of treating an individual who has a WT1-expressing tumor or preventing development of a WT1-expressing tumor comprising administering an amount of a vaccine effective to slow growth of, reduce, or eliminate WT1-expressing tumors, wherein the vaccine comprises a protein comprising an amino acid sequence selected from the group consisting of: SEQ ID NO:2 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:2 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO: 2 without the leader sequence, SEQ ID NO: 4 without the leader sequence, a fragment comprising at least 90% of the entire length of SEQ ID NO:4 without the leader sequence, an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence, and a fragment comprising at least 90% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO: 4 without the leader sequence.
18 . The method of claim 17 , wherein the protein comprises the amino acid sequence as set forth in SEQ ID NO:2 without the leader sequence.