title: A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma.
abstract: The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA-A2(+)  immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes (CTL) against HLA-A2(+)  MM cells. We identified a novel immunogenic HLA-A2-specific CS1(239-247)  (SLFVLGLFL) peptide, which induced CS1-specific CTL (CS1-CTL) to MM cells. The CS1-CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL. CS1(239-247)  peptide-specific CD8(+)  T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and γ-interferon (IFN-γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO(+) CCR7(-) /CD3(+) CD8(+) ) within CS1-CTL showed a higher level of CD107a degranulation and IFN-γ production as compared to effector cells (CD45RO(-) CCR7(-) /CD3(+) CD8(+) ) against HLA-A2(+)  primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA-A2-specific CS1(239-247)  peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Jooeun
authors.initials: J
authors.lastname: Bae
authors.forename: Weihua
authors.initials: W
authors.lastname: Song
authors.forename: Robert
authors.initials: R
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: Daley
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D009842:Oligopeptides / Q000276:immunology* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D011971:Receptors, Immunologic; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family