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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1103-1112.
Prepublished online as a Blood First Edition Paper on October 5, 2006; DOI 10.1182/blood-2006-04-014480.
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Submitted April 3, 2006
Accepted September 7, 2006
Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation
Djordje Atanackovic*, Julia Arfsten, Yanran Cao, Sacha Gnjatic, Frank Schnieders, Katrin Bartels, Georgia Schilling, Christiane Faltz, Christine Wolschke, Judith Dierlamm, Gerd Ritter, Thomas Eiermann, Dieter K Hossfeld, Axel R Zander, Achim A Jungbluth, Lloyd J Old, Carsten Bokemeyer, and Nicolaus Kroger
Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY
Biochemistry and Molecular Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
* Corresponding author; email: d.atanackovic{at}uke.uni-hamburg.de.
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 MM patients (N=55) and healthy donors (N=32) using 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 MM patients (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-151-62 and CD4+ responses against NY-ESO-1121-140 in one of these patients. These allogeneic immune responses were not detectable in pre-transplant 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.

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