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首页> 外文期刊>British Journal of Cancer >T lymphocytes isolated from patients with advanced colorectal cancer are suitable for gene immunotherapy approaches
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T lymphocytes isolated from patients with advanced colorectal cancer are suitable for gene immunotherapy approaches

机译：从晚期大肠癌患者中分离出的T淋巴细胞适用于基因免疫疗法

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Despite improvements in treatment, the 5-year survival for metastatic colorectal cancer remains poor. Novel approaches such as gene immunotherapy are being investigated to improve treatment. Retroviral gene transfer methods have been shown to transduce primary human T lymphocytes effectively resulting in the expression of therapeutic genes. However, a number of defects have been identified in T lymphocytes isolated from patients bearing tumour, which may have critical implications for the development of gene-targeted T cells as an anticancer therapy. To address this issue, primary T lymphocytes were isolated from patients with advanced colorectal cancer and tested for their ability to be transduced and to express subsequently a chimeric immune receptor consisting of a single-chain antibody fragment antigen-binding moiety specific for carcinoembryonic antigen (CEA) fused to the T cell receptor (TCR) CD3ζ chain. In 10 out of 10 patients, T lymphocytes were transduced, expanded in the absence of selection and tested for functional activity against CEA-expressing tumour cells. In each case, functional-specific cytotoxic activity was observed. Negligible activity was found in control cultures. This study highlights the feasibility of patient-derived T lymphocytes as a source of immune cells for autologous gene immunotherapy approaches.
机译：尽管治疗有所改善，但转移性结直肠癌的5年生存率仍然很差。正在研究诸如基因免疫疗法的新方法以改善治疗。逆转录病毒基因转移方法已显示可有效转导原代人T淋巴细胞，从而导致治疗基因的表达。但是，已经从患有肿瘤的患者中分离出的T淋巴细胞中发现了许多缺陷，这可能对开发靶向基因的T细胞作为抗癌疗法具有至关重要的意义。为了解决这个问题，从患有晚期大肠癌的患者中分离了原代T淋巴细胞，并测试了它们的转导能力以及随后表达由癌胚抗原（CEA）特异性的单链抗体片段抗原结合部分组成的嵌合免疫受体的能力。 ）融合到T细胞受体（TCR）CD3ζ链上。在10名患者中，有10名患者转导了T淋巴细胞，在没有选择的情况下进行了扩增，并测试了针对表达CEA的肿瘤细胞的功能活性。在每种情况下，均观察到功能特异性的细胞毒活性。在对照培养物中发现微不足道的活性。这项研究强调了患者来源的T淋巴细胞作为自体基因免疫治疗方法的免疫细胞来源的可行性。

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