title: Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation.
abstract: Immunotherapies using cancer-testis (CT) antigens as targets represent a potentially useful treatment in patients with multiple myeloma (MM) who commonly show recurrent disease following chemotherapy. We analyzed the expression of 11 CT antigens in bone marrow samples from patients with MM (n=55) and healthy donors (n=32) using reverse transcriptase-polymerase chain reaction (RT-PCR). CT antigens were frequently expressed in MM with 56% (MAGEC2), 55% (MAGEA3), 35% (SSX1), 20% (SSX4, SSX5), 16% (SSX2), 15% (BAGE), 7% (NY-ESO-1), and 6% (ADAM2, LIPI) expressing the given antigen. Importantly, CT antigens were not expressed in healthy bone marrow. Analyzing patients with MM (n=66) for antibody responses against MAGEA3, SSX2, and NY-ESO-1, we found strong antibody responses against CT antigens preferentially in patients who had received allogeneic stem cell transplantation (alloSCT). Antibody responses against NY-ESO-1 correlated with NY-ESO-1-specific CD4+ and CD8+ T-cell responses against peptide NY-ESO-1(51-62) and CD4+ responses against NY-ESO-1(121-140) in 1 of these patients. These allogeneic immune responses were not detectable in pretransplantation samples and in the patients' stem cell donors, indicating that CT antigens might indeed represent natural targets for graft-versus-myeloma effects. Immune responses induced by alloSCT could be boosted by active CT antigen-specific immunotherapy, which might help to achieve long-lasting remissions in patients with MM.
authors.affiliation: Department of Oncology/Hematology, Institute for Biochemistry and Molecular Biology, University Medical Center Hamburg-Eppendorf, Germany. d.atanackovic@uke.uni-hamburg.de
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
authors.forename: Julia
authors.initials: J
authors.lastname: Arfsten
authors.forename: Yanran
authors.initials: Y
authors.lastname: Cao
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Frank
authors.initials: F
authors.lastname: Schnieders
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartels
authors.forename: Georgia
authors.initials: G
authors.lastname: Schilling
authors.forename: Christiane
authors.initials: C
authors.lastname: Faltz
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.forename: Judith
authors.initials: J
authors.lastname: Dierlamm
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiermann
authors.forename: Dieter Kurt
authors.initials: DK
authors.lastname: Hossfeld
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
mesh_terms: D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins