Anti-cancer vaccine candidates in specific immunotherapy for bladder carcinoma

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Tumor-rejection antigens and epitope peptides can induce cancer-reactive cytotoxic T lymphocytes (CTLs).
• Specific immunotherapy for bladder carcinoma (BC) requires identification of effective antigens and peptides, particularly for patients with human leukocyte antigen (HLA)-A24+ alleles.

Purpose of the Study:

• To determine the utility of specific antigens and their derived peptides for immunotherapy in HLA-A24+ bladder carcinoma patients.
• To identify candidate antigens expressed in BC cell lines and evaluate their ability to induce peptide-specific CTLs.

Main Methods:

• Examined mRNA expression of cancer-associated antigens in four BC cell lines.
• Assessed the potential of six previously identified antigen-derived peptides to induce CTLs from peripheral-blood mononuclear cells of HLA-A24+ BC patients.
• Investigated the specificity and effector cells of induced CTLs and detected IgG reactivity in patient plasma.

Main Results:

• Three antigens (SART3, MRP3, EZH2) were expressed in three of four BC cell lines.
• Peptides SART3109-118, MRP31293-1301, and EZH2735-742 efficiently induced peptide-specific and BC cell-reactive CTLs from HLA-A24+ BC patients.
• Cytotoxicity was mediated by peptide-specific CD8+ T cells, and IgG reactive to SART3109-118 was frequently detected in BC patient plasma.

Conclusions:

• SART3, MRP3, and EZH2 derived peptides show promise for developing peptide-based immunotherapy in HLA-A24+ bladder carcinoma patients.
• The identified peptides can induce potent and specific anti-tumor immune responses mediated by CD8+ T cells.
• Further development of these peptides could lead to effective immunotherapeutic strategies for bladder cancer.