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* Institute of Research in Biotherapy. Centre Hospitalier Universitaire Montpellier, Montpellier, France;
Institut National de la Santé et de la Recherche Médicale, Unité 475, Montpellier, France;
Université Montpellier, Unité de Formation et de Recherche Médecine, Montpellier, France;
Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany;
¶ Department of Hematology and Clinical Oncology, Centre Hospitalier Universitaire Montpellier, Montpellier, France; and
|| National Center of Tumour Diseases Heidelberg, Heidelberg, Germany
Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Ligue Nationale Contre Le Cancer (équipe labellisée), Paris, France and from Guillaume Espoir (St. Genis Laval, France). It is part of the national program called "Carte d’Identité des Tumeurs" program (CIT) or Tumor Identity Card developed and funded by the Ligue Nationale Contre le Cancer (http://www.ligue-cancer.net).
2 Address correspondence and reprint requests to Dr. Bernard Klein, Institut National de la Santé et de la Recherche Médicale U475, 99 Rue Puech Villa, Montpellier, France. E-mail address: klein{at}montp.inserm.fr
3 Abbreviations used in this paper: MM, multiple myeloma; ABSCT, autologous blood stem cell transplantation; BMPC, bone marrow plasma cell; CT, cancer-testis; CT-X, a CT gene located on chromosome X; EFS, event-free survival; GEP, gene expressing profiling; HDC, high-dose chemotherapy; HMCL, human myeloma cell line; MB, peripheral blood memory B cell; MGUS, monoclonal gammopathy of unknown significance; MMC, multiple myeloma cell; PPC, polyclonal plasmablast.
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  O. C. Goodyear, G. Pratt, A. McLarnon, M. Cook, K. Piper, and P. Moss Differential pattern of CD4+ and CD8+ T-cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma Blood, October 15, 2008; 112(8): 3362 - 3372. [Abstract] [Full Text] [PDF]
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