Cloning of a new gene encoding an antigen recognized by melanoma-specific HLA-A24-restricted tumor-infiltrating lymphocytes.
Cloning of a new gene encoding an antigen recognized by melanoma-specific HLA-A24-restricted tumor-infiltrating lymphocytes.
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克隆编码黑色素瘤特异性 HLA-A24 限制性肿瘤浸润淋巴细胞识别抗原的新基因。
DOI：
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发表时间：
1995
影响因子：
4.4
通讯作者：
S. A. Rosenberg
中科院分区：
文献类型：
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作者：
P. Robbins;M. El;Yong F Li;S. Topalian;L. Rivoltini;Kazuyasu Sakaguchi;Ettore Appella;Yutaka Kawakami;S. A. Rosenberg
肿瘤特异性T细胞在介导转移性黑色素瘤消退中的作用已由患者对肿瘤浸润淋巴细胞（TIL）治疗的临床反应提出。最近分离出了一些由I类限制性黑色素瘤特异性T细胞识别的Ag，这增加了开发改进疗法的希望。在这项研究中，我们报告的肿瘤抗原识别的T细胞从黑色素瘤患者888的克隆。以前，我们报道，TIL 888，从这个病人的肿瘤生长，识别酪氨酸酶在HLA-A24限制的方式。当输注到自体患者体内时，该线导致多个转移灶完全消退。三年后，第二个TIL系，TIL 1290，从复发的盆腔肿瘤中分离出来。将TIL 888和TIL 1290细胞系的混合物输注到患者体内导致残余腹部肿块完全消退，并且患者在2年后保持无病。以HLA-A24限制性方式识别黑素瘤的TIL 1290细胞系不能识别酪氨酸酶。然后使用TIL 1290筛选888黑色素瘤cDNA文库，并分离出与序列数据库中发现的任何抗原都不对应的抗原。该基因被称为p15，被发现在多种正常组织中表达，并且发现由TIL 1290识别的肽表位代表非突变基因的产物。筛选额外的cDNA库导致分离刺激TIL 1290的第二克隆。该克隆似乎也代表了p15基因的转录本，表明该基因可能编码TIL 1290识别的主要Ag。
The role of tumor-specific T cells in mediating the regression of metastatic melanoma has been suggested by the clinical response of patients to treatment with tumor-infiltrating lymphocytes (TIL). A number of Ags recognized by class I-restricted melanoma-specific T cells have recently been isolated, raising the hope that this will lead to the development of improved therapies. In this study, we report the cloning of a tumor Ag recognized by T cells from melanoma patient 888. Previously, we reported that TIL 888, grown from the tumor of this patient, recognized tyrosinase in an HLA-A24-restricted fashion. This line, when infused into the autologous patient, resulted in complete regression of multiple metastases. Three years later, a second TIL line, TIL 1290, was isolated from a recurrent pelvic tumor. Infusion of a mixture of TIL 888 and TIL 1290 cell lines into the patient resulted in complete regression of a residual abdominal mass and the patient remains disease-free 2 yr later. The TIL 1290 cell line, which recognized melanoma in an HLA-A24-restricted manner, failed to recognize tyrosinase. TIL 1290 was then used to screen an 888 melanoma cDNA library, and an Ag was isolated that did not correspond to any found in sequence databases. This gene, termed p15, was found to be expressed in a variety of normal tissues, and a peptide epitope recognized by TIL 1290 was found to represent the product of an nonmutated gene. Screening of additional cDNA pools resulted in the isolation of a second clone which stimulated TIL 1290. This clone also appeared to represent a transcript of the p15 gene, indicating that this gene may encode the predominant Ag recognized by TIL 1290.