Dhodapkar Madhav V, Osman Keren, Teruya-Feldstein Julie, Filippa Daniel, Hedvat Cyrus V, Iversen Kristin, Kolb Denise, Geller Matthew D, Hassoun Hani, Kewalramani Tarun, Comenzo Raymond L, Coplan Keren, Chen Yao-Tseng, Jungbluth Achim A
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
Cancer Immun. 2003 Jul 23;3:9.
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.
癌胚/睾丸（CT）抗原在多种恶性肿瘤中表达，但除睾丸生殖细胞外，在正常组织中不表达。CT抗原蛋白在恶性血液病中的表达尚未得到明确描述。我们使用以下单克隆抗体（mAb），通过免疫组织化学检测了29例恶性血液病患者中一组CT抗原蛋白的表达：抗MAGE-A1的mAb MA454、抗MAGE-A3的mAb M3H67、抗MAGE-A4的mAb 57B、抗CT7/MAGE-C1的mAb CT7-33和抗NY-ESO-1的mAb ES121。我们在29例患者中的27例肿瘤中检测到至少一种CT抗原。在大多数情况下，MAGE-A1、-A3、-A4和NY-ESO-1的表达模式是异质性的，在<25%的肿瘤细胞中显示染色。单克隆抗体CT7-33和M3H67显示出最高的免疫反应发生率。重要的是，通过流式细胞术在一些骨髓瘤细胞表面也可检测到CT-7，在一例浆细胞瘤病例中通过免疫组织化学也可检测到。相对于其他队列，III期髓外浆细胞瘤或高危骨髓瘤患者中CT抗原的表达更高。这些数据表明，CT抗原可能在恶性血液病中具有重要的生物学意义，并且CT-7可能是骨髓瘤基于T细胞以及可能基于抗体介导的免疫治疗的合适靶点。
