WT1 vaccine
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: a nucleic acid sequence that encodes the protein set forth by SEQ ID NO:2 without the leader sequence, a nucleic acid sequence that encodes a fragment comprising at least 95% of the entire length of SEQ ID NO:2 without the leader sequence, a nucleic acid sequence that encodes a protein that is at least 98% identical to SEQ ID NO:2 without the leader sequence, a nucleic acid sequence that encodes a fragment comprising at least 95% of the entire length of a protein that is at least 98% identical to SEQ ID NO:2 without the leader sequence, a nucleic acid sequence that encodes the protein set forth by SEQ ID NO:4 without the leader sequence, a nucleic acid sequence that encodes a fragment comprising at least 95% of the entire length of SEQ ID NO:4 without the leader sequence, a nucleic acid sequence that encodes a protein that is at least 98% identical to SEQ ID NO:4 without the leader sequence, and a nucleic acid sequence that encodes a fragment comprising at least 95% of the entire length of a protein that is at least 98% identical to SEQ ID NO:4 without the leader sequence.
2. The isolated nucleic acid molecule of claim 1 , wherein the one or more nucleic acid sequences are selected from the group consisting of: SEQ ID NO: 1 without the leader sequence, a fragment comprising at least 95% 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 without the leader sequence, a fragment comprising at least 95% of the entire length of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 without the leader sequence, SEQ ID NO: 3 without the leader sequence, a fragment comprising at least 95% 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 without the leader sequence, and a fragment comprising at least 95% of the entire length of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:3 without the leader sequence.
3. The isolated nucleic acid molecule of claim 1 wherein said molecule is incorporated into a plasmid or a viral vector.
4. A composition comprising one or more of the nucleic acid molecules of claim 1 .
5. A vaccine comprising one or more of the nucleic acid molecules of claim 1 .
6. A method of treating an individual who has a WT1-expressing tumor comprising administering the vaccine of claim 5 in an amount effective to slow growth of, reduce or eliminate the WT1 expressing tumors.
7. An isolated 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 95% 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 without the leader sequence, a fragment comprising at least 95% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:2 without the leader sequence, SEQ ID NO:4 without the leader sequence, a fragment comprising at least 95% 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 without the leader sequence, and a fragment comprising at least 95% of the entire length of an amino acid sequence that is at least 98% identical to SEQ ID NO:4 without the leader sequence.
8. The vaccine of claim 5 , further comprising a protein wherein the protein is selected from the group consisting of a protein comprising an amino acid sequence that is at least about 95% identical to the protein set forth by SEQ ID NO:2 over the entire length of SEQ ID NO:2 without the leader sequence; and a protein comprising an amino acid sequence that is at least about 95% identical to the protein set forth by SEQ ID NO:4 over the entire length of SEQ ID NO:4 without the leader sequence.
9. The vaccine of claim 5 , wherein the one or more nucleic acid molecules are comprised in an expression vector.
10. The vaccine of claim 5 , further comprising a pharmaceutically acceptable excipient.
11. The vaccine of claim 5 , further comprising an adjuvant.
12. The isolated nucleic acid molecule of claim 1 , wherein the one or more nucleic acid sequences is the nucleic acid sequence set forth in SEQ ID NO:1 without the leader sequence.
13. The isolated nucleic acid molecule of claim 1 , wherein the one or more nucleic acid sequences is the nucleic acid sequence set forth in SEQ ID NO:3 without the leader sequence.
14. The isolated protein of claim 7 , wherein the amino acid sequence is the amino acid sequence set forth in SEQ ID NO:2 without the leader sequence.
15. The isolated protein of claim 7 , wherein the amino acid sequence is the amino acid sequence set forth in SEQ ID NO:4 without the leader sequence.
16. A vaccine comprising the isolated protein of claim 7 .
17. The vaccine of claim 16 , wherein the isolated protein comprises the amino acid sequence set forth in SEQ ID NO:2 without the leader sequence.
18. The vaccine of claim 16 , wherein the isolated protein comprises the amino acid sequence set forth in SEQ ID NO:4 without the leader sequence.