title: A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients.
abstract: We evaluated a cocktail of HLA-A2-specific peptides including heteroclitic XBP1 US184-192 (YISPWILAV), heteroclitic XBP1 SP367-375 (YLFPQLISV), native CD138260-268 (GLVGLIFAV) and native CS1239-247 (SLFVLGLFL), for their ability to elicit multipeptide-specific cytotoxic T lymphocytes (MP-CTLs) using T cells from smoldering multiple myeloma (SMM) patients. Our results demonstrate that MP-CTLs generated from SMM patients' T cells show effective anti-MM responses including CD137 (4-1BB) upregulation, CTL proliferation, interferon-γ production and degranulation (CD107a) in an HLA-A2-restricted and peptide-specific manner. Phenotypically, we observed increased total CD3(+)CD8(+) T cells (>80%) and cellular activation (CD69(+)) within the memory SMM MP-CTL (CD45RO(+)/CD3(+)CD8(+)) subset after repeated multipeptide stimulation. Importantly, SMM patients could be categorized into distinct groups by their level of MP-CTL expansion and antitumor activity. In high responders, the effector memory (CCR7(-)CD45RO(+)/CD3(+)CD8(+)) T-cell subset was enriched, whereas the remaining responders' CTL contained a higher frequency of the terminal effector (CCR7(-)CD45RO(-)/CD3(+)CD8(+)) subset. These results suggest that this multipeptide cocktail has the potential to induce effective and durable memory MP-CTL in SMM patients. Therefore, our findings provide the rationale for clinical evaluation of a therapeutic vaccine to prevent or delay progression of SMM to active disease.
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bae
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA [3] VA Boston Healthcare System, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Prabhala
authors.affiliation: Johns Hopkins School of Public Health, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Voskertchian
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.affiliation: Tufts University School of Medicine, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Maguire
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Richardson
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Dranoff
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA [3] VA Boston Healthcare System, Boston, MA, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Munshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000276:immunology*; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000276:immunology*; D000071701:Regulatory Factor X Transcription Factors; D053668:Syndecan-1 / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000939:Epitopes; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D000071701:Regulatory Factor X Transcription Factors; C508241:SDC1 protein, human; D053668:Syndecan-1; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C076687:CS1 peptide