EphA2 T-cell epitopes and uses therefor
AssigneesMedImmune, LLC, University of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsWalter J Storkus, Michael S Kinch
Life of this patent
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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.
Claims45
A purified EphA2 T-cell epitope that binds to a major histocompatibility complex (“MHC”) Class II molecule, wherein the epitope is a peptide that consists of 9 to 35 contiguous amino acid residues of native human EphA2 (SEQ ID NO:2), and wherein the EphA2 T-cell epitope has a predicted binding score of greater than 39 for the MHC Class II molecule HLA-DRβ1*0401 as determined using the Southwood algorithm.
A purified EphA2 T-cell epitope that binds at an MHC Class II molecule, wherein the EphA2 T-cell epitope has an amino acid sequence selected from the group consisting of:
- 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);
- MQNIMNDMP (SEQ ID NO:2, residues 55-63);
- DLMQNIMNDMPIYMYS (SEQ ID NO:2, residues 53-68);
- IMGQFSHHN (SEQ ID NO:2, residues 666-674);
- IVMWEVMTY (SEQ ID NO:2, residues 805-813);
- IVTSVTCEQ (SEQ ID NO:2, residues 360-368);
- IRLPSTSGS (SEQ ID NO:
- 2, residues 893-901;
- VELRWTPPQ (SEQ ID NO:2, residues 344-352);
- LRWTPPQDS (SEQ ID NO:2, residues 346-354);
- VVLLLVLAG (SEQ ID NO:
- 2, residues 545-553);
- ILVNSNLVC (SEQ ID NO:2, residues 745-753);
- and MNYTFTVEA (SEQ ID NO:2, residues 406-414).
Dependencies are inferred from the claim text.