EPHA2 t-cell epitope agonists and uses therefore
EphA2 T-cell epitope are provided herein. The epitopes include peptides corresponding to specific fragments of human EphA2 protein containing one or more T-cell epitopes, and conservative derivatives thereof. The EphA2 T-cell epitopes are useful in an assay, such as an ELISPOT assay, that may be used to determine and/or quantify a patient's immune responsiveness to EphA2. The epitopes also are useful in methods of modulating a patient's immune reactivity to EphA2, which has substantial utility as a treatment for cancers that overexpress EphA2, such as renal cell carcinoma (RCC). The EphA2 epitopes also can be used to vaccinate a patient against EphA2, by in vivo or ex vivo methods.
1. An isolated peptide that consists of 9-35 amino acid residues, wherein said isolated peptide comprises the peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75),
where said peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75):
(i) has up to one conservative amino acid substitution within the conservative substitution groups (a) S and T, (b) L, I and V, and (c) E and D; and
(ii) retains the ability to stimulate a T-cell immune response to EphA2 as determined by ELISPOT assay.
2. The isolated peptide of claim 1 , comprising the peptide VLLLVLAGV (SEQ ID NO:2, residues 546-554).
3. The isolated peptide of claim 1 , comprising the peptide IMGQFSHHN (SEQ ID NO:2, residues 666-674).
4. The isolated peptide of claim 1 , comprising the peptide YSVCNVMSG (SEQ ID NO:2, residues 67-75).
5. A vaccine formulation comprising an isolated peptide that consists of 9-35 amino acid residues, wherein said isolated peptide comprises the peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75),
where said peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75):
(i) has up to one conservative amino acid substitution within the conservative substitution groups (a) S and T, (b) L, I and V, and (c) E and D; and
(ii) retains the ability to stimulate a T-cell immune response to EphA2 as determined by ELISPOT assay, and a pharmaceutically acceptable carrier.
6. The vaccine formulation of claim 5 , where the isolated peptide comprises the peptide VLLLVLAGV (SEQ ID NO:2, residues 546-554).
7. The vaccine formulation of claim 5 , where the isolated peptide comprises the peptide IMGQFSHHN (SEQ ID NO:2, residues 666-674).
8. The vaccine formulation of claim 5 , where the isolated peptide comprises the peptide YSVCNVMSG (SEQ ID NO:2, residues 67-75).
9. The vaccine formulation of claim 5 , further comprising an adjuvant.
10. The vaccine formulation of claim 6 , further comprising an adjuvant.
11. The vaccine formulation of claim 7 , further comprising an adjuvant.
12. The vaccine formulation of claim 8 , further comprising an adjuvant.
13. The vaccine formulation of claim 5 , wherein the isolated peptide comprises a second peptide where said second peptide is not an EphA2 peptide and is immunogenic.
14. The vaccine formulation of claim 6 , wherein the isolated peptide comprises a second peptide where said second peptide is not an EphA2 peptide and is immunogenic.
15. The vaccine formulation of claim 7 , wherein the isolated peptide comprises a second peptide where said second peptide is not an EphA2 peptide and is immunogenic.
16. The vaccine formulation of claim 8 , wherein the isolated peptide comprises a second peptide where said second peptide is not an EphA2 peptide and is immunogenic.
17. A method of eliciting an immune response to EphA2 in a subject, comprising administering, to the subject, an effective amount of an isolated peptide that consists of 9-35 amino acid residues and wherein said isolated peptide comprises the peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75),
where said peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75):
(i) has up to one conservative amino acid substitution within the conservative substitution groups (a) S and T, (b) L, I and V, and (c) E and D; and
(ii) retains the ability to stimulate a T-cell immune response to EphA2 as determined by ELISPOT assay.
18. A method of eliciting an immune response to EphA2 in a subject, comprising administering, to the subject, an effective amount of a vaccine formulation comprising an isolated peptide that consists of 9-35 amino acid residues, wherein said isolated peptide comprises the peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75),
where said peptide of VLLLVLAGV (SEQ ID NO:2, residues 546-554), IMGQFSHHN (SEQ ID NO:2, residues 666-674) or YSVCNVMSG (SEQ ID NO:2, residues 67-75):
(i) has up to one conservative amino acid substitution within the conservative substitution groups (a) S and T, (b) L, I and V, and (c) E and D; and
(ii) retains the ability to stimulate a T-cell immune response to EphA2 as determined by ELISPOT assay, and a pharmaceutically acceptable carrier.