title: 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.
authors: Dana-Farber Cancer Institute, Boston, MA, USA.
authors: Jooeun
authors: J
authors: Bae
authors: Yu-Tzu
authors: YT
authors: Tai
authors: Kenneth C
authors: KC
authors: Anderson
authors: Nikhil C
authors: NC
authors: Munshi
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020014:K562 Cells; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D053668:Syndecan-1 / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D053668:Syndecan-1; D022223:Vaccines, Subunit