EphA2 T-cell epitopes and uses therefor
OwnerWalter J. Storkus, Michael S. Kinchinventors
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Abstract
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.
Claims9
A method of treating cancer in a patient in need thereof, said method comprising administering to the patient a therapeutically effective amount of a purified EphA2 T-cell epitope, wherein said EphA2 T-cell epitope binds to an MHC Class II molecule, wherein said EphA2 T-cell epitope is a peptide that consists of 9 to 35 contiguous amino acid residues of native human EphA2 (SEQ ID NO:
- 2), and wherein said EphA2 T-cell epitope has a predicted binding score of greater than 39 for the MHC Class II molecule HLA-DRβ1*0402 as determined using the Southwood algorithm.
A method of treating cancer, said method comprising administering to a patient in need thereof a therapeutically effective amount of a purified EphA2 T-cell epitope or a purified polypeptide comprising an EphA2 T-cell epitope and a second amino acid sequence,
- wherein the EphA2 T-cell epitope is a peptide that:
- (i) consists of 9 to 35 contiguous amino acid residues of native human EphA2 (SEQ ID NO:
- 2), and
- (ii) has:
- (x) a predicted binding score of 98 or below for the major histocompatibility complex (“MHC”) Class I molecule HLA-A2 as determined using the NIH BIMAS “HLA Peptide Binding Predictions” software, or
- (y) an amino acid sequence identified using the ProPred software as a sequence that binds to MHC Class II molecule HLA-DRβ1*0402,
- wherein said EphA2 T-cell epitope and said second amino acid sequence are not contiguous to each other in the amino acid sequence of SEQ ID NO:
- 2.
A method of eliciting an immune response to EphA2 in a patient, said method comprising administering to the patient an effective amount of a purified EphA2 T-cell epitope or a purified polypeptide comprising an EphA2 T-cell epitope and a second amino acid sequence,
- wherein the EphA2 T-cell epitope is a peptide that:
- (i) consists of 9 to 35 contiguous amino acid residues of native human EphA2 (SEQ ID NO:
- 2), and
- (ii) has:
- (x) a predicted binding score of 98 or below for the major histocompatibility complex (“MHC”) Class I molecule HLA-A2 as determined using the NIH BIMAS “HLA Peptide Binding Predictions” software, or
- (y) an amino acid sequence identified using the ProPred software as a sequence that binds to MHC Class II molecule HLA-DRβ1*0402,
- wherein said EphA2 T-cell epitope and said second amino acid sequence are not contiguous to each other in the amino acid sequence of SEQ ID NO:
- 2.
A method of treating cancer in a patient in need thereof, said method comprising administering to the patient a therapeutically effective amount of a purified EphA2 T-cell epitope, wherein said EphA2 T-cell epitope is a peptide that consists of 9 to 35 contiguous amino acid residues of native human EphA2 (SEQ ID NO:
- 2), and is selected from the group consisting of:
- TLADFDPRV (SEQ ID NO:
- 2, residues 883-891);
- VLLLVLAGV (SEQ ID NO:
- 2, residues 546-554);
- VLAGVGFFI (SEQ ID NO:
- 2, residues 550-558);
- IMNDMPIYM (SEQ ID NO:
- 2, residues 58-66);
- SLLGLKDQV (SEQ ID NO:
- 2, residues 961-969);
- WLVPIGQCL (SEQ ID NO:
- 2, residues 253-261);
- LLWGCALAA (SEQ ID NO:
- 2, residues 12-20);
- GLTRTSVTV (SEQ ID NO:
- 2, residues 391-399);
- NLYYAESDL (SEQ ID NO:
- 2, residues 120-128);
- KLNVEERSV (SEQ ID NO:
- 2, residues 162-170);
- IMGQFSHHN (SEQ ID NO:
- 2, residues 666-674);
- YSVCNVMSG (SEQ ID NO:
- 2, residues 67-75);
- MQNIMNDMP (SEQ ID NO:
- 2, residues 55-63);
- EAGIMGQFSHHNIIR (SEQ ID NO:
- 2, residues 663-677);
- PIYMYSVCNVMSG (SEQ ID NO:
- 2, residues 63-75);
- DLMQNIMNDMPIYMYS (SEQ ID NO:
- 2, residues 53-68);
- DLMQNIMNDMPIYMYSVCNVMSG (SEQ ID NO:
- 2, residues 53-75);
- and
- VLLLVLAGVGFFI (SEQ ID NO:
- 2, residues 546-558).
Dependencies are inferred from the claim text.