...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cancer biology & therapy >Adoptive immunotherapy of lung cancer with immobilized anti-TCRgammadelta antibody-expanded human gammadelta T-cells in peripheral blood.
【24h】

Adoptive immunotherapy of lung cancer with immobilized anti-TCRgammadelta antibody-expanded human gammadelta T-cells in peripheral blood.

机译：固定化抗TCRgammadelta抗体可扩增外周血中人γT细胞的过继免疫疗法。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Lung cancer is the leading cause of cancer death. The prognosis of metastatic lung cancer is poor. We had previously established the condition to expand human gammadelta T-cells in peripheral blood and tumor infiltrating T lymphocytes with immobilized anti-TCRgammadelta antibody. Such expanded gammadelta T-cells exhibited potent cytolytic activity to different tumor cell lines in vitro and in vivo. Here we further characterized human anti-TCRgammadelta-expanded gammadelta T-cells and tested their antitumor function in treatment for lung cancer in nude mice. In comparison to gammadelta T-cells activated by phosphoantigen, a prevalent Vdelta2 stimulus, anti-TCRgammadelta-expanded gammadelta T-cells had similar major subset with Vdelta2 phenotype, but they had about 10% of Vdelta1 subsets and high percentages of CD27(-)CD45RA(-) and CD27(-)CD45RA(+) effector cells. They also displayed TCR diversity of multiple clones. Importantly, the antibody-expanded gammadelta T-cells showed strong cytotoxicity to three lung cancer cell lines and had significant antitumor effect on squamous lung carcinoma in nude mice. The ex vivo anti-TCRgammadelta-expanded gammadelta T-cells prolonged tumor bearing mouse survival and slowed down tumor growth, with similar efficacy to chemotherapy by cis-platinum. Moreover, adoptively transferred human gammadelta T-cells survived for more than one month in vivo. Finally, gammadelta T-cells derived from 11 cases of patients with lung cancer had proliferative activity after TCRgammadelta ligandation, displayed marked cytotoxicity to lung cancer cells and expressed cytotoxicity- or antitumor activity-related molecules, such as perforin, granzyme A and B, Fas ligand, TNFalpha and IFNgamma. Taken together, our finding suggests that anti-TCRgammadelta expanded gammadelta T-cells may be used as cellular therapy in treatment of lung cancer.
机译：肺癌是癌症死亡的主要原因。转移性肺癌的预后很差。我们以前已经确定了用固定的抗TCRgammadelta抗体在外周血和浸润肿瘤的T淋巴细胞中扩增人γT细胞的条件。这种扩增的γ-T细胞在体外和体内对不同的肿瘤细胞系表现出有效的细胞溶解活性。在这里，我们进一步表征了人类抗TCRgammadelta扩展的γT细胞，并测试了其在裸鼠肺癌治疗中的抗肿瘤功能。与被磷酸抗原激活的γδT细胞（一种普遍的Vdelta2刺激）相比，抗TCRγγδ扩增的γδT细胞具有与Vdelta2表型相似的主要亚群，但它们具有约10％的Vdelta1亚群和高百分比的CD27（-） CD45RA（-）和CD27（-）CD45RA（+）效应细胞。他们还显示了多个克隆的TCR多样性。重要的是，抗体扩增的Gammadelta T细胞对三种肺癌细胞系显示出强大的细胞毒性，并对裸鼠的鳞状肺癌具有显着的抗肿瘤作用。离体抗TCRγδ扩增的γT细胞延长了荷瘤小鼠的存活并减慢了肿瘤的生长，其疗效与顺铂化疗相似。而且，过继转移的人γT细胞在体内存活超过一个月。最后，来自11例肺癌患者的伽马T细胞在TCRγ配体后具有增殖活性，对肺癌细胞显示出明显的细胞毒性，并表达与细胞毒性或抗肿瘤活性相关的分子，例如穿孔素，颗粒酶A和B，Fas配体，TNFalpha和IFNgamma。综上所述，我们的发现表明抗TCRγδ扩增的γδT细胞可以用作治疗肺癌的细胞疗法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号