Lendvai Nikoletta, Gnjatic Sacha, Ritter Erika, Mangone Michael, Austin Wayne, Reyner Karina, Jayabalan David, Niesvizky Ruben, Jagannath Sundar, Bhardwaj Nina, Chen-Kiang Selina, Old Lloyd J, Cho Hearn Jay
New York University Cancer Institute, New York University School of Medicine, New York, NY, USA.
Cancer Immun. 2010 Jan 29;10:4.
The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.
I型黑色素瘤抗原基因（MAGE）蛋白CT7（MAGE-C1）和MAGE-A3在多发性骨髓瘤（MM）中普遍表达，其表达与浆细胞增殖增加及临床预后不良相关。它们属于肿瘤相关蛋白的癌胚抗原（CTAg）组，其中一些可在癌症患者中引发自发免疫反应。CT7和MAGE-A3是骨髓瘤治疗性肿瘤疫苗有前景的抗原靶点；因此，确定它们在MM患者中是否具有免疫原性至关重要。我们分析了浆细胞发育异常患者（MM、意义未明的单克隆丙种球蛋白病（MGUS）和华氏巨球蛋白血症（WM））针对CTAgs的细胞免疫和体液免疫反应。通过自体细胞免疫测定法检测，4例未经治疗的MM患者中有2例的骨髓淋巴细胞表现出CT7特异性细胞免疫反应，这是癌症患者中首次报道的针对CT7的此类免疫反应。通过ELISA筛选24例患者的血清，检测其针对CTAgs的体液免疫反应。2例MM患者显示出阳性滴度，1例针对MAGE-A1，另1例针对SSX1。这些数据表明，CTAgs，尤其是CT7，在MM患者中具有免疫原性，值得作为MM免疫治疗的靶点进一步探索。
