Abstract
6554 Background: CT7 (MAGE-C1) is a member of the Cancer-Testis (CT) family of tumor-associated antigens. CT antigen-based vaccines are currently under investigation in clinical trials. It has previously been demonstrated that myeloma cells lines and primary myeloma cells express CT antigens. Therefore, CT antigens may be suitable targets for multiple myeloma vaccine immunotherapy. To characterize CT antigen expression in primary myeloma cells, a comprehensive survey of patient specimens was undertaken to identify optimal target candidates. Methods: Bone marrow biopsy and aspirate samples were obtained from 27 patients with multiple myeloma or monoclonal gammopathy of uncertain significance (MGUS). Plasma cells were purified from bone marrow aspirates by anti-CD138 magnetic bead selection. RT-PCR analysis was performed for MAGE-A1, -A3, -A4, -A10, LAGE-1, NY-ESO-1 and CT7. Protein expression was studied by immunohistochemistry (IHC) for the following antigens (using the following mAbs): MAGE-A1 (mAb MA454), MAGE-A3 (mAb M3H67), MAGE-A4 (mAb 57B), CT7 (mAb CT733), NY-ESO-1 (mAb E978 & ES121). Results: CT7, MAGE-A3, and NY-ESO-1 were the most frequently detected CT antigens in multiple myeloma, as shown in the table below. Surprisingly, CT7 mRNA and protein were detected in all stage III multiple myeloma patients. Of note, 13/18 samples demonstrated positive IHC for CT7 in more than 25% of malignant cells. CT7 was also detected in a subset of earlier stage and MGUS samples. Conclusions: CT antigens are variably expressed in primary myeloma cells. CT7 appears to be the most widely expressed CT antigen in the malignant plasma cells of multiple myeloma and is a potential universal target for vaccine immunotherapy. There is good correlation between CT7 mRNA and protein expression. The common expression of CT7 in multiple myeloma also suggests the possibility that it plays a pathogenic role in this disease. No significant financial relationships to disclose.
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