Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma.
Identification of MAGE-C1 (CT-7) epitopes for T-cell therapy of multiple myeloma.
复制标题
DOI：
10.1007/s00262-011-1009-3
复制
发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Riddell SR
中科院分区：
文献类型：
--
作者：
Anderson LD Jr;Cook DR;Yamamoto TN;Berger C;Maloney DG;Riddell SR
多发性骨髓瘤是无法治愈的标准疗法，但易受t细胞介导的移植物对抗骨髓瘤效应异体干细胞移植后。我们试图鉴定可能用于骨髓瘤t细胞免疫治疗的骨髓瘤特异性抗原。MAGE-C1 （CT-7）是一种癌睾丸抗原，在约70%的骨髓瘤患者中由肿瘤细胞表达，并在高达93%的CT-7+骨髓瘤患者中引起体液反应。CT-7的CD8+ t细胞表位尚未被描述，因此我们使用了一种新的基于细胞的疫苗，结合反向免疫学和HLA-A2转基因小鼠的免疫，鉴定了CT-7的三个免疫原性表位，这些表位可以被人CD8+ t细胞识别。识别其中两种肽的CT-7特异性t细胞能够识别骨髓瘤细胞以及CT-7基因转导的肿瘤细胞，这表明这些表位是由肿瘤细胞自然加工和呈现的。这是鉴定MAGE-C1 （CT-7）的免疫原性CD8+ t细胞表位的第一篇报道，这是骨髓瘤中最常表达的癌睾丸抗原，这些表位可能是骨髓瘤或其他CT-7+恶性肿瘤的疫苗接种或t细胞治疗的有希望的候选靶点。
Multiple myeloma is incurable with standard therapies but is susceptible to a T-cell-mediated graft versus myeloma effect after allogeneic stem cell transplantation. We sought to identify myeloma-specific antigens that might be used for T-cell immunotherapy of myeloma. MAGE-C1 (CT-7) is a cancer-testis antigen that is expressed by tumor cells in >70% of myeloma patients and elicits a humoral response in up to 93% of patients with CT-7+ myeloma. No CD8+ T-cell epitopes have been described for CT-7, so we used a combination of reverse immunology and immunization of HLA-A2 transgenic mice with a novel cell-based vaccine to identify three immunogenic epitopes of CT-7 that are recognized by human CD8+ T-cells. CT-7-specific T-cells recognizing two of these peptides are able to recognize myeloma cells as well as CT-7 gene-transduced tumor cells, demonstrating that these epitopes are naturally processed and presented by tumor cells. This is the first report of the identification of immunogenic CD8+ T-cell epitopes of MAGE-C1 (CT-7), which is the most commonly expressed cancer-testis antigen found in myeloma, and these epitopes may be promising candidate targets for vaccination or T-cell therapy of myeloma or other CT-7+ malignancies.
登录
查看更多内容
影响因子：
158.5
作者：
Bruno, Benedetto;Rotta, Marcello;Boccadoro, Mario
通讯作者：
Boccadoro, Mario
DOI：
10.1073/pnas.202491499
发表时间：
2002-10-01
影响因子：
11.1
作者：
Dhodapkar, MV;Krasovsky, J;Olson, K
通讯作者：
Olson, K
影响因子：
20.3
作者：
Bensinger, WI;Buckner, CD;Appelbaum, FR
通讯作者：
Appelbaum, FR
影响因子：
20.3
作者：
Berger, C;Flowers, ME;Riddell, SR
通讯作者：
Riddell, SR
影响因子：
15.3
作者：
Dhodapkar, KM;Krasovsky, J;Dhodapkar, MV
通讯作者：
Dhodapkar, MV