A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames.

A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames.
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乳腺和黑色素瘤共有的肿瘤抗原:T 细胞对从不同开放阅读框翻译的抗原肽的反应。

DOI:
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发表时间:
1998
影响因子:
4.4
通讯作者:
Steven A. Rosenberg
Steven A. Rosenberg
中科院分区:
医学2区
文献类型:
--
作者:
Rongfu Wang;Samuel L. Johnston;Gang Zeng;S. Topalian;D. Schwartzentruber;Steven A. Rosenberg

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将TIL 586沿着IL-2输注到患有转移性黑色素瘤的自体患者中导致肿瘤的客观消退。在这里,我们报告说,筛选的cDNA文库从586 mel细胞系使用CTL克隆来自TIL 586导致分离的基因,CAG-3(癌抗原基因3)。序列分析显示CAG-3编码一个与NY-ESO-1相同的开放阅读框,NY-ESO-1最近被报道能被来自食管癌患者的自体血清识别。因此,NY-ESO-1似乎是Ab和T细胞介导的应答的免疫靶标。值得注意的是,NY-ESO-1特异性CTL克隆能够识别两个HLA-A31阳性的新鲜和培养的乳腺肿瘤。据我们所知,这是第一次直接证明肿瘤特异性CTL克隆可以识别乳腺癌和黑色素瘤肿瘤细胞。从NY-ESO-1的正常开放阅读框中鉴定了一个10聚体抗原肽ESO 10 -53(ASGPGGGAPR),其基于其对HLA-A31阳性靶细胞的细胞因子释放和特异性裂解的敏感性的能力。有趣的是,用NY-ESO-1致敏的另外两个CTL克隆识别来自相同基因的替代开放阅读框的两个重叠抗原肽。这些发现表明,CTL同时响应于从相同基因的正常和替代阅读框架翻译的两种不同的基因产物。了解这种机制,替代阅读框架的翻译可能有重要的意义,在肿瘤免疫学。
Infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Here, we report that screening a cDNA library from the 586mel cell line using CTL clones derived from TIL586 resulted in the isolation of a gene, CAG-3 (cancer Ag gene 3). Sequence analysis revealed that CAG-3 encodes an open reading frame identical to NY-ESO-1, which was recently reported to be recognized by autologous serum from a patient with esophageal cancer. Thus, NY-ESO-1 appears to be an immune target for both Ab- and T cell-mediated responses. Significantly, NY-ESO-1-specific CTL clones were capable of recognizing two HLA-A31-positive fresh and cultured breast tumors. To our knowledge, this represents the first direct demonstration that tumor-specific CTL clones can recognize both breast and melanoma tumor cells. A 10-mer antigenic peptide ESO10-53 (ASGPGGGAPR) was identified from the normal open reading frame of NY-ESO-1 based on its ability to sensitize HLA-A31-positive target cells for cytokine release and specific lysis. Interestingly, two additional CTL clones that were sensitized with NY-ESO-1 recognized two overlapping antigenic peptides derived from an alternative open reading frame of the same gene. These findings indicate that CTLs simultaneously responded to two different gene products translated from the normal and alternative reading frames of the same gene. Understanding of this mechanism by which the alternative reading frame is translated may have important implications in tumor immunology.
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