Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cancer Immunol Immunother. 2011 Jul;60(7):985-97. doi: 10.1007/s00262-011-1009-3. Epub 2011 Apr 3.
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.
多发性骨髓瘤用标准疗法无法治愈，但在同种异体干细胞移植后，可发生 T 细胞介导的移植物抗骨髓瘤效应。我们试图鉴定骨髓瘤特异性抗原，这些抗原可能用于多发性骨髓瘤的 T 细胞免疫治疗。MAGE-C1（CT-7）是一种癌-睾丸抗原，在>70%的骨髓瘤患者的肿瘤细胞中表达，并在高达 93%的 CT-7（+）骨髓瘤患者中引发体液反应。目前尚未描述 CT-7 的 CD8+T 细胞表位，因此我们使用反向免疫学和用新型基于细胞的疫苗免疫 HLA-A2 转基因小鼠的组合，鉴定了 CT-7 的三个免疫原性表位，这些表位可被人 CD8+T 细胞识别。能够识别其中两种肽的 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递的。这是首次鉴定 MAGE-C1（CT-7）的免疫原性 CD8+T 细胞表位的报告，CT-7 是骨髓瘤中最常见表达的癌-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标。
