Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation.
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.
Atanackovic
Djordje
D
Department of Oncology/Hematology, Institute for Biochemistry and Molecular Biology, University Medical Center Hamburg-Eppendorf, Germany. d.atanackovic@uke.uni-hamburg.de
Arfsten
Julia
J
Cao
Yanran
Y
Gnjatic
Sacha
S
Schnieders
Frank
F
Bartels
Katrin
K
Schilling
Georgia
G
Faltz
Christiane
C
Wolschke
Christine
C
Dierlamm
Judith
J
Ritter
Gerd
G
Eiermann
Thomas
T
Hossfeld
Dieter Kurt
DK
Zander
Axel R
AR
Jungbluth
Achim A
AA
Old
Lloyd J
LJ
Bokemeyer
Carsten
C
Kröger
Nicolaus
N
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*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins