title: Cancer-testis antigen SLLP1 represents a promising target for the immunotherapy of multiple myeloma.
abstract: BACKGROUND
  Most patients with multiple myeloma (MM) will relapse after an initial response and eventually succumb to their disease. This is due to the persistence of chemotherapy-resistant tumor cells in the patients' bone marrow (BM) and immunotherapeutic approaches could contribute to eradicating these remaining cells. We evaluated SLLP1 as a potential immunotherapeutic target for MM.
  
  
  METHODS
  We determined SLLP1 expression in myeloma cell lines and 394 BM samples from myeloma patients (n = 177) and BM samples from healthy donors (n = 11). 896 blood samples and 64 BM samples from myeloma patients (n = 263) and blood from healthy donors (n = 112) were analyzed for anti-SLLP1 antibodies. Seropositive patients were evaluated regarding SLLP1-specific T cells.
  
  
  RESULTS
  Most cell lines showed SLLP1 RNA and protein expression while it was absent from normal BM. Of 177 patients 41% evidenced SLLP1 expression at least once during the course of their disease and 44% of newly diagnosed patients were SLLP1-positive. Expression of SLLP1 was associated with adverse cytogenetics and with negative prognostic factors including the patient's age, number of BM-infiltrating plasma cells, serum albumin, β2-microglobulin, creatinine, and hemoglobin. Among patients treated with allogeneic stem cell transplantation those with SLLP1 expression showed a trend towards a reduced overall survival. Spontaneous anti-SLLP humoral immunity was detectable in 9.5% of patients but none of the seropositive patients evidenced SLLP1-specific T cells. However, antigen-specific T cells could readily be induced in vitro after stimulation with SLLP1.
  
  
  CONCLUSIONS
  SLLP1 represents a promising target for the immunotherapy of MM, in particular for the adoptive transfer of T cell receptor-transduced T cells.
authors.affiliation: Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Sara.Yousef@hci.utah.edu.|Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Sara.Yousef@hci.utah.edu.
authors.forename: Sara
authors.initials: S
authors.lastname: Yousef
authors.affiliation: Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. johanna.heise@busybirds.org.
authors.forename: Johanna
authors.initials: J
authors.lastname: Heise
authors.affiliation: Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. nnlajmi@gmail.com.
authors.forename: Nesrine
authors.initials: N
authors.lastname: Lajmi
authors.affiliation: Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. katrinbartels@hotmail.com.
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartels
authors.affiliation: Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. nkroeger@uke.de.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Tim.Luetkens@hci.utah.edu.|Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Tim.Luetkens@hci.utah.edu.
authors.forename: Tim
authors.initials: T
authors.lastname: Luetkens
authors.affiliation: Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. djordje.atanackovic@hci.utah.edu.|Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. djordje.atanackovic@hci.utah.edu.|Multiple Myeloma Program and Cancer Immunotherapy, Division of Hematology and Hematologic Malignancies, University of Utah/Huntsman Cancer Institute, Room HCI 4265, 2000 Circle of Hope Drive, Salt Lake City, UT, 84112, USA. djordje.atanackovic@hci.utah.edu.
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000917:Antibody Formation / Q000276:immunology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007519:Isoantigens / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010641:Phenotype; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry; D029589:Seminal Plasma Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D000939:Epitopes; D007074:Immunoglobulin G; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell; C490560:SPACA3 protein, human; D029589:Seminal Plasma Proteins