Identification of Cyclophilin B-derived Peptides Capable of Inducing Histocompatibility Leukocyte Antigen-A2-restricted and Tumor-specific Cytotoxic T Lymphocytes

Abstract

We recently suggested that cyclophilin B (Cyp‐B) is a tumor antigen recognized by histocompatibility leukocyte antigen (HLA)‐A24‐restricted and tumor‐specific cytotoxic T lymphocytes (CTLs). In this study, we tried to identify Cyp‐B‐derived epitopes, which can induce HLA‐A2‐restricted and tumor‐specific CTLs in cancer patients. The tumor‐infiltrating lymphocytes (TILs) from an HLA‐A0207 patient with colon cancer were found to respond to COS‐7 cells when co‐transfected with the Cyp‐B gene and either HLA‐A0201, ‐A0206, or ‐A0207 cDNA. These TILs contained CTLs capable of recognizing either the Cyp‐B129–138 or the Cyp‐B172–179 peptide among 28 different peptides, all of which were prepared based on the HLA‐A2 binding motif. Both Cyp‐B peptides possessed the ability to induce tumor‐specific CTLs in HLA‐A2+ cancer patients. Cyp‐B172–180 (v), which is a 9‐mer peptide with valine added at the C terminus, showed no clear superiority over the parental Cyp‐B172‐179 peptide in an in vitro sensitization experiment. In vitro ‐sensitized T cells with these peptides responded to cancer cells in an HLA‐A2‐restricted manner. These two Cyp‐B peptides could be useful for specific immunotherapy of HLA‐A2+ cancer patients.