Coulie P G, Weynants P, Lehmann F, Herman J, Brichard V, Wölfel T, Van Pel A, De Plaen E, Brasseur F, Boon T
Ludwig Institute for Cancer Research, Brussels Branch, Belgium.
J Immunother Emphasis Tumor Immunol. 1993 Aug;14(2):104-9. doi: 10.1097/00002371-199308000-00004.
In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by transfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone. The gene that transferred the expression of the antigen was named MAGE-1. It is a new gene, silent in normal tissues with the exception of testis, but expressed in several types of tumors. The antigen recognized by the CTL clone is a nonapeptide derived from the protein encoded by gene MAGE-1, and presented by the HLA class I molecule HLA-A1. Using two other antimelanoma CTL clones, we identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on this type of tumors. The identification of these tumor rejection antigens open new possibilities for the specific immunotherapy of cancer.
为了确定细胞溶解型T淋巴细胞（CTL）在自体肿瘤上识别的抗原，我们从自体混合淋巴细胞肿瘤细胞培养物中获得了肿瘤特异性CTL克隆。通过将肿瘤的基因组DNA转染到黑色素瘤的抗原缺失变异体中，分离出了在黑色素瘤上表达的肿瘤排斥抗原的编码基因。根据转染体刺激CTL克隆释放肿瘤坏死因子的能力来鉴定转染体。转移抗原表达的基因被命名为MAGE-1。它是一个新基因，在除睾丸外的正常组织中不表达，但在几种类型的肿瘤中表达。CTL克隆识别的抗原是一种九肽，由MAGE-1基因编码的蛋白质衍生而来，并由HLA I类分子HLA-A1呈递。使用另外两个抗黑色素瘤CTL克隆，我们确定酪氨酸酶基因编码这种类型肿瘤上由HLA-A2呈递的抗原。这些肿瘤排斥抗原的鉴定为癌症的特异性免疫治疗开辟了新的可能性。
