Abstract
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.
Highlights
Expression of known CT genes in patients with MM, patients with monoclonal gammopathy of unknown significance (MGUS), and in human myeloma cell lines (HMCL) and normal cells according to the present/absent call provided by Affymetrix HG-U133 set arrays
Twenty-seven CT genes were not expressed in plasma cells from patients with MGUS and eight were expressed in at least one of 12 samples: SPANXB, CT45, GAGE1– 8, SPACA3, DDX43/HAGE, MORC, MAGE-C1, and KM-HN-1
One aim of this study was to provide an overview of the expression of known CT genes in primary MM cells (MMC) from newly diagnosed patients
Summary
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. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in MM; 2) to estimate their prognosis value; and 3) to provide appropriate selection strategies for clinical vaccination trials
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