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:
(i) a nucleic acid sequence that encodes the protein set forth by SEQ ID NO:2;
(ii) a nucleic acid sequence that encodes a fragment of the protein set forth by SEQ ID NO:2 wherein the fragment comprises at least 90% of the entire length of the protein set forth by SEQ ID NO:2;
(iii) a nucleic acid sequence that encodes a protein that is at least 98% identical to the protein set forth by SEQ ID NO:2 over the entire length of SEQ ID NO:2;
(iv) a nucleic acid sequence that encodes a fragment of a protein that is at least 98% identical to the protein set forth by SEQ ID NO: 2 wherein the length of the fragment is at least 90% of the entire length of the protein set forth by SEQ ID NO:2;
(v) a nucleic acid sequence that encodes the protein set forth by SEQ ID NO:4;
(vi) a nucleic acid sequence that encodes a fragment of SEQ ID NO:4 wherein the fragment comprises at least 90% of the entire length of the protein set forth by SEQ ID NO:4;
(vii) a nucleic acid sequence that encodes a protein that is at least 98% identical to the protein set forth by SEQ ID NO:4 over the entire length of SEQ ID NO:4; and
(viii) a nucleic acid sequence that encodes a fragment of a protein that is 98% identical to the protein set forth by SEQ ID NO: 4 wherein the length of the fragment is at least 90% of the entire length of the protein set forth by SEQ ID NO:4.
2. An isolated nucleic acid molecule comprising one or more nucleic acid sequences selected from the group consisting of:
(i) SEQ ID NO: 1;
(ii) a fragment of SEQ ID NO:1 wherein the fragment comprises at least 90% of the entire length of SEQ ID NO:1;
(iii) a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 over the entire length of SEQ ID NO:1;
(iv) a fragment of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:1 wherein the length of the fragment is at least 90% of the entire length of SEQ ID NO:1;
(v) SEQ ID NO: 3;
(vi) a fragment of SEQ ID NO:3 wherein the fragment comprises at least 90% of the entire length of SEQ ID NO:3;
(vii) a nucleic acid sequence that is at least 98% identical to SEQ ID NO:3 over the entire length of SEQ ID NO:3; and
(viii) a fragment of a nucleic acid sequence that is at least 98% identical to SEQ ID NO:3 wherein the length of the fragment is at least 90% of the entire length SEQ ID NO:3.
3. The isolated nucleic acid molecule of claim 1 , wherein said isolated nucleic acid molecule is incorporated into a plasmid or a viral vector.
4. A composition comprising the isolated nucleic acid molecule of claim 1 .
5. A composition comprising the isolated nucleic acid molecule of claim 2 .
6. A vaccine comprising the isolated nucleic acid molecule of claim 1 .
7. A vaccine comprising the isolated nucleic acid molecule of claim 2 .
8. A method of treating an individual who has a WT1-expressing tumor comprising administering the vaccine of claim 6 in an amount effective to slow growth of, reduce or eliminate WT1-expressing tumors.
9. An isolated protein comprising an amino acid sequence selected from the group consisting of:
(i) SEQ ID NO:2,
(ii) a fragment of SEQ ID NO:2 wherein the fragment comprises at least 90% of the entire length of SEQ ID NO:2,
(iii) an amino acid sequence that is at least 98% identical to SEQ ID NO:2 over the entire length of SEQ ID NO:2,
(iv) a fragment of an amino acid sequence that is at least 98% identical to SEQ ID NO:2 wherein the length of the fragment is at least 90% of the entire length of SEQ ID NO:2,
(v) SEQ ID NO:4,
(vi) a fragment of SEQ ID NO:4 wherein the fragment comprises at least 90% of the entire length of SEQ ID NO:4,
(vii) an amino acid sequence that is at least 98% identical to SEQ ID NO:4 over the entire length of SEQ ID NO:4, and
(viii) a fragment of an amino acid sequence that is 98% identical to SEQ ID NO: 4 wherein the length of the fragment is at least 90% of the entire length SEQ ID NO:4.
10. A vaccine comprising a nucleic acid molecule, wherein the nucleic acid molecule is selected from the group consisting of
a nucleic acid molecule comprising a nucleic acid sequence that is at least about 90% identical to SEQ ID NO: 1 over the entire length of SEQ ID NO: 1; and
a nucleic acid molecule comprising a nucleic acid sequence that is at least about 90% identical to SEQ ID NO: 3 over the entire length of SEQ ID NO:3.
11. The vaccine of claim 10 , 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 90% identical to SEQ ID NO: 2 over the entire length of SEQ ID NO:2; and
a protein comprising an amino acid sequence that is at least about 90% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO:4.
12. The vaccine of claim 10 , wherein the nucleic acid molecule is comprised in an expression vector.
13. The vaccine of claim 10 , further comprising a pharmaceutically acceptable excipient.
14. The vaccine of claim 10 , further comprising an adjuvant.
15. A vaccine comprising a nucleic acid molecule, wherein the nucleic acid molecule is selected from the group consisting of
a nucleic acid molecule encoding a protein comprising an amino acid sequence that is at least about 90% identical to SEQ ID NO: 2 over the entire length of SEQ ID NO:2; and
a nucleic acid molecule encoding a protein comprising an amino acid sequence that is at least about 90% identical to SEQ ID NO: 4 over the entire length of to SEQ ID NO:4.
16. The vaccine of claim 15 , 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 90% identical to SEQ ID NO: 2 over the entire length of SEQ ID NO:2; and
a protein comprising an amino acid sequence that is at least about 90% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO:4.
17. The vaccine of claim 15 wherein the nucleic acid molecule is comprised in an expression vector.
18. The vaccine of claim 15 , further comprising a pharmaceutically acceptable excipient.
19. The vaccine of claim 15 , further comprising an adjuvant.
20. An isolated nucleic acid molecule comprising the nucleic acid sequence set forth by SEQ ID NO:1.
21. An isolated nucleic acid molecule comprising the nucleic acid sequence set forth by SEQ ID NO:3.
22. An isolated protein comprising the amino acid sequence set forth by SEQ ID NO:2.
23. An isolated protein comprising the amino acid sequence set forth by SEQ ID NO:4.
24. A vaccine comprising an antigen, wherein the antigen is encoded by SEQ ID NO:1 or SEQ ID NO:3.
25. The vaccine of claim 24 , wherein the antigen is encoded by SEQ ID NO:1.
26. The vaccine of claim 24 , wherein the antigen is encoded by SEQ ID NO:3.
27. A vaccine comprising an antigen, wherein the antigen comprises the amino acid sequence set forth by SEQ ID NO:2 or SEQ ID NO:4.
28. The vaccine of claim 27 , wherein the antigen comprises the amino acid sequence set forth by SEQ ID NO:2.
29. The vaccine of claim 27 , wherein the antigen comprises the amino acid sequence set forth by SEQ ID NO:4.
30. A vaccine 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 90% identical to SEQ ID NO: 2 over the entire length of SEQ ID NO:2; and
a protein comprising an amino acid sequence that is at least about 90% identical to SEQ ID NO: 4 over the entire length of SEQ ID NO:4.
31. The vaccine of claim 30 , wherein the protein comprises the amino acid sequence set forth by SEQ ID NO:2.
32. The vaccine of claim 30 , wherein the protein comprises the amino acid sequence set forth by SEQ ID NO:4.