title: Myeloma-specific multiple peptides able to generate cytotoxic T lymphocytes: a potential therapeutic application in multiple myeloma and other plasma cell disorders.
abstract: OBJECTIVE
  The efficacy of peptide vaccines may be enhanced by stimulating immune cells with multiple peptides derived from distinct tumor-associated antigens. We have evaluated the heteroclitic XBP1-US(184-192) (YISPWILAV), heteroclitic XBP1-SP(367-375) (YLFPQLISV), native CD138(260-268) (GLVGLIFAV), and native CS1(239-247) (SLFVLGLFL) peptides, which have strong HLA-A2 affinity and immunogenicity in combination, for their ability to elicit multiple myeloma antigen-specific responses.
  
  
  METHODS
  Multipeptide-specific cytotoxic T lymphocytes (MP-CTL) were generated by the stimulation of CD3(+) T lymphocytes from HLA-A2(+) individuals with either autologous mature dendritic cells or T2 cells pulsed with a cocktail of these four peptides.
  
  
  RESULTS
  The peptide cocktail did not compromise tumor antigen-specific activity of CTLs. MP-CTLs displayed increased total, effector memory (CCR7(-)CD45RO(+)), and activated (CD69(+)) CD3(+)CD8(+) T lymphocytes. In addition, MP-CTL showed IFN-γ production, cell proliferation, and cytotoxicity against HLA-A2(+) multiple myeloma cells, including cells of HLA-A2(+) patients with multiple myeloma. Importantly, MP-CTLs showed specific responses in functional assays to each relevant peptide but not to an irrelevant HLA-A2-specific CMV pp65 (NLVPMVATV) peptide.
  
  
  CONCLUSIONS
  These results highlight the potential therapeutic application of vaccination with a cocktail of HLA-A2-specific peptides to induce CTLs with a broad spectrum of immune responses against multiple myeloma antigens.
authors: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: Jooeun
authors: J
authors: Bae
authors: Robert
authors: R
authors: Smith
authors: John
authors: J
authors: Daley
authors: Naoya
authors: N
authors: Mimura
authors: Yu-Tzu
authors: YT
authors: Tai
authors: Kenneth C
authors: KC
authors: Anderson
authors: Nikhil C
authors: NC
authors: Munshi
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000071701:Regulatory Factor X Transcription Factors; D053668:Syndecan-1 / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D022223:Vaccines, Subunit / Q000627:therapeutic use; D000071717:X-Box Binding Protein 1
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D015789:HLA-A2 Antigen; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D000071701:Regulatory Factor X Transcription Factors; C508241:SDC1 protein, human; D053668:Syndecan-1; D014157:Transcription Factors; D022223:Vaccines, Subunit; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C076687:CS1 peptide