EphA2 as target of anticancer immunotherapy: identification of HLA-A*0201-restricted epitopes

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• EphA2 (Eck) is a tyrosine kinase receptor overexpressed in multiple human cancers, including breast, colon, lung, prostate, gastric carcinoma, and melanoma.
• EphA2 is not typically found in nonmalignant tissues, making it a potential target for cancer therapies.

Purpose of the Study:

• To validate EphA2 as a tumor antigen recognized by CD8+ T lymphocytes using a reverse immunology approach.
• To identify and characterize HLA-A*0201-restricted epitopes derived from EphA2.

Main Methods:

• Identification of HLA-A*0201-restricted peptides from EphA2.
• Analysis of peptide binding affinity and stabilization of HLA-A*0201 molecules.
• Immunization of HLA-A*0201-transgenic HHD mice with selected peptides.
• Testing of T cell responses against EphA2-expressing tumor cells and peripheral blood mononuclear cells from healthy donors and cancer patients.

Main Results:

• Two peptides, EphA2(58) and EphA2(550), demonstrated high affinity for HLA-A*0201 and were immunogenic in HHD mice.
• Murine CTLs and T cells from healthy donors recognized EphA2-positive tumor cells in an HLA-A*0201-restricted manner.
• EphA2-specific CD8+ T cells were detected in the peripheral blood of prostate cancer patients, indicating natural T cell responses.

Conclusions:

• EphA2 is a tumor rejection antigen, and the identified peptides EphA2(58) and EphA2(550) are naturally processed.
• These peptides represent promising candidates for broad-spectrum tumor immunotherapy targeting EphA2-expressing cancers.
• The findings support the development of T cell-based immunotherapies against EphA2-positive malignancies.