Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes targeting multiple myeloma and other plasma cell disorders

Abstract

The development of an immunotherapeutic strategy targeting CD138 antigen could potentially represent a new treatment option for multiple myeloma (MM). This study evaluated the immune function of CD138 peptide-specific cytotoxic T lymphocytes (CTL), generated ex vivo using an HLA-A2-specific CD138 epitope against MM cells. A novel immunogenic HLA-A2-specific CD138 260-268 (GLVGLIFAV) peptide was identified from the full-length protein sequence of the CD138 antigen, which induced CTL specific to primary CD138 + MM cells. The peptide-induced CD138-CTL contained a high percentage of CD8 + activated/memory T cells with a low percentage of CD4 + T cell and naive CD8 + T cell subsets. The CTL displayed HLA-A2-restricted and CD138 antigen-specific cytotoxicity against MM cell lines. In addition, CD138-CTL demonstrated increased degranulation, proliferation and γ-interferon secretion to HLA-A2 +/CD138 + myeloma cells, but not HLA-A2 -/CD138 + or HLA-A2 +/CD138 - cells. The immune functional properties of the CD138-CTL were also demonstrated using primary HLA-A2 +/CD138 + cells isolated from myeloma patients. In conclusion, a novel immunogenic CD138 260-268 (GLVGLIFAV) peptide can induce antigen-specific CTL, which might be useful for the treatment of MM patients with peptide-based vaccine or cellular immunotherapy strategies. © 2011 Blackwell Publishing Ltd.