Jungbluth Achim A, Ely Scott, DiLiberto Maurizio, Niesvizky Ruben, Williamson Barbara, Frosina Denise, Chen Yao-Tseng, Bhardwaj Nina, Chen-Kiang Selina, Old Lloyd J, Cho Hearn Jay
New York Branch, Ludwig Institute for Cancer Research, New York, NY, USA.
Blood. 2005 Jul 1;106(1):167-74. doi: 10.1182/blood-2004-12-4931. Epub 2005 Mar 10.
Multiple myeloma is a malignancy of plasma cells. Vaccine immunotherapy is among the novel therapeutic strategies under investigation for this disease. To identify myeloma-associated antigens as potential targets for vaccine immunotherapy, we surveyed a comprehensive panel of bone marrow specimens from patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma for expression of cancer-testis (CT) antigens. Immunohistochemistry (IHC) demonstrated that 82% of stage-III myeloma specimens expressed the CT antigen CT7 (also known as melanoma antigen C1 [MAGE-C1]) and 70% expressed MAGE-A3/6. Messenger RNA for CT7 and MAGE-A family members was detected in 87% and 100% of stage-III samples, respectively. CT7 protein expression increased with advanced stage of disease. Higher levels of CT7 and MAGE-A3/6 proteins also correlated with elevated plasma-cell proliferation. These results show that CT7 and MAGE-A3/6 are promising myeloma-associated antigens for application in vaccine immunotherapy. Furthermore, the common expression and correlation with proliferation suggest a possible pathogenic role for these proteins in myeloma.
多发性骨髓瘤是浆细胞的恶性肿瘤。疫苗免疫疗法是针对该疾病正在研究的新型治疗策略之一。为了确定骨髓瘤相关抗原作为疫苗免疫疗法的潜在靶点,我们对来自意义未明的单克隆丙种球蛋白病(MGUS)和多发性骨髓瘤患者的一组全面的骨髓标本进行了癌症睾丸(CT)抗原表达情况的调查。免疫组织化学(IHC)显示,82%的III期骨髓瘤标本表达CT抗原CT7(也称为黑色素瘤抗原C1 [MAGE-C1]),70%表达MAGE-A3/6。在87%和100%的III期样本中分别检测到CT7和MAGE-A家族成员的信使RNA。CT7蛋白表达随疾病进展而增加。CT7和MAGE-A3/6蛋白的较高水平也与浆细胞增殖增加相关。这些结果表明,CT7和MAGE-A3/6是有望用于疫苗免疫疗法的骨髓瘤相关抗原。此外,共同表达以及与增殖的相关性表明这些蛋白在骨髓瘤中可能具有致病作用。