title: 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.
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.
authors.affiliation: Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA. dhodapm@mail.rockefeller.edu
authors.forename: Madhav V
authors.initials: MV
authors.lastname: Dhodapkar
authors.forename: Keren
authors.initials: K
authors.lastname: Osman
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Daniel
authors.initials: D
authors.lastname: Filippa
authors.forename: Cyrus V
authors.initials: CV
authors.lastname: Hedvat
authors.forename: Kristin
authors.initials: K
authors.lastname: Iversen
authors.forename: Denise
authors.initials: D
authors.lastname: Kolb
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Geller
authors.forename: Hani
authors.initials: H
authors.lastname: Hassoun
authors.forename: Tarun
authors.initials: T
authors.lastname: Kewalramani
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Comenzo
authors.forename: Keren
authors.initials: K
authors.lastname: Coplan
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009367:Neoplasm Staging; D010954:Plasmacytoma / Q000175:diagnosis / Q000378:metabolism*; D011379:Prognosis; D014176:Protein Biosynthesis
chemical_list: D000951:Antigens, Neoplasm; C473332:CT7 antigen, human; C104948:CTAG1B protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins