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首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Functional detection of epithelial cell adhesion molecule specific cytotoxic T lymphocytes in patients with lung cancer, colorectal cancer and in healthy donors.
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Functional detection of epithelial cell adhesion molecule specific cytotoxic T lymphocytes in patients with lung cancer, colorectal cancer and in healthy donors.

机译:上皮细胞粘附的功能检测特定的细胞毒性T淋巴细胞分子患者肺癌、结直肠癌和在健康的捐赠者。

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摘要

Epithelial cell adhesion molecule (Ep-CAM) derived antigenic peptides have been identified that can be recognized by cytotoxic T lymphocytes (CTL) in a major histocompatibility complex (MHC) class I restricted fashion. Thus, altered expression of Ep-CAM in a variety of human tumors might render a potential target for T cell mediated therapy. We have examined, whether the novel HLA-A*0201 restricted peptide ILYENNVIT (184-192) corresponding to Ep-CAM and one heteroclitic modified variant peptide previously demonstrated to be immunogenic in the human system can elicit antigen specific CTL responses in HLA-A2 positive patients with history of Ep-CAM expressing cancer of lung and colon. Specific CTL recognition of T2 target cells pulsed with the native peptide as well as of the lung cancer cell line A549 indicates that an appropriate T cell repertoire can be expanded from peripheral blood from patients in clinical remission and with advanced cancer. Despite an overall low frequency, peptide specific precursor CTLs could be readily expanded from peripheral blood from 6/8 patients that were diagnosed previously with Ep-CAM expressing lung cancer and 4/8 control individuals (2/5 healthy donors and 2/3 colon cancer patients). CTLs from three of five lung cancer patients tested also lyzed the HLA-A2(+) and Ep-CAM expressing lung cancer cell line A549. We did not detect an increased frequency of pCTLs after peripheral blood monocytes (PBMCs) were stimulated with the heteroclitic compound peptide. The results of our study indicate that Ep-CAM specific precursor CTL can be expanded in vitro and a specific T cell response against this epitope can be elicited in patients at various stages of lung cancer.
机译:上皮细胞粘附分子(Ep-CAM)抗原肽已确定可以被认可的细胞毒性T淋巴细胞(CTL)我主要组织相容性复合体(MHC)类受限制的时尚。Ep-CAM多种人类肿瘤可能呈现一个潜在的目标T细胞介导的药物治疗。我们已经检查,是否新的抗原* 0201限制肽ILYENNVIT (184 - 192)对应于Ep-CAM和一个不规则变化的之前修改变体肽在人类系统可以引起免疫原性在hla a2抗原特异性CTL反应积极患者癌症Ep-CAM表达的历史肺癌和结肠癌。靶细胞脉冲与原生肽的肺癌细胞系A549表明一个适当的T细胞剧目可以扩展从外周血吗患者在临床缓解期和先进癌症。特定的前体ctl可以很容易扩展从6/8患者外周血诊断之前Ep-CAM表示肺癌症(2/5和4/8控制个人健康捐助者和2/3结肠癌患者)。三个五个肺癌患者也进行了测试lyzed hla a2(+)和Ep-CAM表达肺癌症细胞系A549。增加后pCTLs外围的频率血液单核细胞(PBMCs)是刺激的不规则变化的复合肽。研究表明,Ep-CAM特定的前驱细胞毒性t淋巴细胞可以扩展体外特异性T细胞针对这种抗原决定基可以引起的反应肺癌病人的不同阶段。

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