Anti-cancer vaccine candidates in specific immunotherapy for bladder carcinoma

Abstract

We have previously identified numerous tumor-rejection antigens and their epitope peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes (CTLs) in patients with various types of cancer. In the present study, we attempted to determine which antigens and their peptides are useful in specific immunotherapy for bladder carcinoma (BC) patients, especially those with human leukocyte antigen (HLA)-A24+ alleles. The mRNA expression of a panel of cancer-associated antigens was examined regarding four BC cell lines. As a result, three candidate antigens, including SART3, multidrug resistance-associated protein 3 (MRP3), and polycomb group protein enhancer of zeste homolog 2 (EZH2), were expressed in three of four BC cell lines. Thereafter, antigen-derived peptides which we reported to induce cancer-reactive CTLs from HLA-A24+ patients with various types of cancer were examined for their potential to induce CTLs from peripheral-blood mononuclear cells of HLA-A24+ BC patients. Among these antigen-derived six peptides, SART3109-118, MRP31293-1301, and EZH2 735-742 peptides efficiently induced peptide-specific and BC cell-reactive CTLs from HLA-A24+ BC patients. The cytotoxicity against BC cells was dependent on peptide-specific CD8+ T cells. IgG reactive to the SART3109-118 peptide was frequently detected in the plasma of BC patients. This information could facilitate the development of effective peptide-based immunotherapy for HLA-A24+ BC patients.