Gibbs P, Hutchins A M, Dorian K T, Vaughan H A, Davis I D, Silvapulle M, Cebon J S
Ludwig Institute for Cancer Research and the Medical Oncology Department of the Austin and Repatriation Medical Centre, Heidelberg, Australia.
Melanoma Res. 2000 Jun;10(3):259-64.
MAGE proteins have been identified as potential specific targets for cancer vaccination. Although MAGE-6 and MAGE-12 were originally identified in malignant melanoma there are no studies reporting the frequency of expression of these antigens in this malignancy. These are of relevance particularly for MAGE-6 as recent studies have identified CTL activity against several epitopes. We have studied MAGE-1, -2, -3, -4, -6 and -12 gene expression using reverse transcription-polymerase chain reaction in 47 melanoma samples and 11 melanoma cell lines established from these tumours. The tumour samples expressed MAGE-12 (74%) and MAGE-6 (64%) mRNA at much higher frequencies than the other MAGE genes. MAGE-12 and MAGE-6 were expressed at the highest frequencies, relative to the other MAGE antigens, in early stage lesions. The frequency of expression of all the MAGE genes was found to be higher in samples from metastatic deposits compared to those from locoregional disease. The cell lines all expressed the same or more MAGE antigens than the tumours from which they were derived. In only one cell line was expression of a MAGE antigen lost. Certain recurring patterns of MAGE expression were observed in the tumour samples. MAGE-6 and/or -12 expression were detected in all of those 26 tumour samples that were positive for one or more of MAGE-1, -2, -3 and -4. Twenty of these 26 samples expressed both antigens. These findings suggest that protocols targeting MAGE-12 and -6 would permit many more patients to be included into clinical cancer vaccination trials.
黑色素瘤相关抗原(MAGE)蛋白已被确定为癌症疫苗接种的潜在特异性靶点。尽管MAGE - 6和MAGE - 12最初是在恶性黑色素瘤中发现的,但尚无研究报道这些抗原在该恶性肿瘤中的表达频率。这些研究具有重要意义,特别是对于MAGE - 6,因为最近的研究已经确定了针对几种表位的细胞毒性T淋巴细胞(CTL)活性。我们使用逆转录 - 聚合酶链反应研究了47例黑色素瘤样本和从这些肿瘤建立的11个黑色素瘤细胞系中MAGE - 1、-2、-3、-4、-6和-12基因的表达。肿瘤样本中MAGE - 12(74%)和MAGE - 6(64%)mRNA的表达频率远高于其他MAGE基因。相对于其他MAGE抗原,MAGE - 12和MAGE - 6在早期病变中的表达频率最高。发现与局部区域疾病的样本相比,转移灶样本中所有MAGE基因的表达频率更高。细胞系表达的MAGE抗原与它们所源自的肿瘤相同或更多。仅在一个细胞系中MAGE抗原的表达缺失。在肿瘤样本中观察到某些MAGE表达的重复模式。在26个对MAGE - 1、-2、-3和-4中的一种或多种呈阳性的肿瘤样本中,均检测到MAGE - 6和/或-12的表达。这26个样本中有20个表达了这两种抗原。这些发现表明,针对MAGE - 12和-6的方案将允许更多患者纳入临床癌症疫苗接种试验。