Cancer Immunity 3:9 (2003)

Expression of cancer/testis (CT) antigens MAGE-A1, MAGE-A3, MAGE-A4, CT-7, and NY-ESO-1 in malignant gammopathies is heterogeneous and correlates with site, stage and risk status of disease

Madhav V. Dhodapkar^{1, 2}, Keren Osman¹, Julie Teruya-Feldstein³, Daniel Filippa³, Cyrus V. Hedvat³, Kristin Iversen⁴, Denise Kolb⁴, Matthew D. Geller¹, Hani Hassoun², Tarun Kewalramani², Raymond L. Comenzo², Keren Coplan⁴, Yao-Tseng Chen⁵, and Achim A. Jungbluth⁴

¹Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY
²Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
³Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
⁴Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering Cancer Center, New York, NY
⁵Department of Pathology, Weill Medical College of Cornell University, New York, NY

Keywords: human, multiple myeloma, plasmacytoma, tumor antigens, immunohistochemistry, prognosis

Abstract

Cancer/testis (CT) antigens are expressed in several malignant tumors, but not in normal tissues except for testicular germ cells. The expression of CT antigenic proteins in malignant gammopathies has not been characterized. We examined the expression of a panel of CT antigenic proteins in 29 patients with malignant gammopathies by immunohistochemistry using the following monoclonal antibodies (mAbs): mAb MA454 to MAGE-A1, mAb M3H67 to MAGE-A3, mAb 57B to MAGE-A4, mAb CT7-33 to CT7/MAGE-C1 and mAb ES121 to NY-ESO-1. We could detect at least one CT antigen in tumors from 27 of 29 patients. The expression pattern of MAGE-A1, -A3, -A4 and NY-ESO-1 is heterogeneous in most cases, revealing staining in <25% of the tumor cells. Monoclonal antibodies CT7-33 and M3H67 show the highest incidence of immunoreactivity. Importantly, CT-7 can also be detected on the surface of some myeloma cells by flow cytometry, and in one plasmacytoma case by immunohistochemistry. Expression of CT antigens is greater in patients with stage III extramedullary plasmacytoma or high-risk myeloma relative to other cohorts. These data suggest that CT antigens may have important biological implications in malignant gammopathies and that CT-7 may be a suitable target for T cell-based and possibly antibody-mediated immunotherapy of myeloma.