Longitudinale Untersuchung der Expression von Cancer/Testis-Antigenen im Knochenmark von Patienten mit Multiplem Myelom

Abstract

BACKGROUND AND OBJECTIVES: Reliable data on the persistence of the ex-pression of tumor antigens over time and consequent analyses of its impact on the clinical course of malignancies are crucial for their evaluation as clinical parameters and immunotherapeutic targets. This study represents the first longitudinal investiga-tion of Cancer-Testis (CT) antigen expression in Multiple Myeloma (MM) patients and its relevance for therapeutic, diagnostic, and predictive clinical use. DESIGN AND METHODS: 330 bone marrow (BM) samples from 129 MM patients and 40 samples from healthy BM donors were screened for the expression of 4 CT antigens (MAGE-C1/CT7, MAGE-C2/CT10, MAGE-A3, and SSX-2) by conventional RT-PCR. Selected patient samples were analyzed by real-time PCR and Western Blot. Finally, statistical analyses of experimental and clinical data were carried out. RESULTS: CT antigens were frequently and persistently expressed, indicating that down-regulation of these immunogenic targets does not represent a common tumor escape mechanism in patients with multiple myeloma. Strong correlations of CT anti-gen expression levels with the clinical course of myeloma patients as indicated by the number of bone marrow-residing plasma cells and peripheral paraprotein levels further suggest a potential role for CT antigens as independent tumor markers. Inte-restingly, antigen MAGE-C1/CT7 was found to represent an extraordinarily frequent coexpression partner, indicating a potential role as a gatekeeper gene. In addition, MAGE-C1/CT7 represented an indicator of early relapse and dramatically reduced survival in patients following allogeneic stem cell transplantation (alloSCT). CONCLUSIONS: Analyzing a large number of patients with MM, this study estab-lished essential parameters endorsing the use of CT antigens as immunotherapeutic target structures and for the first time suggested the use of the mRNA expression of distinct CT antigens as diagnostic and predictive markers.