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首页> 外文期刊>Cellular immunology >Engineered cells for costimulatory enhancement combined with IL-21 enhance the generation of PD-1-disrupted CTLs for adoptive immunotherapy
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Engineered cells for costimulatory enhancement combined with IL-21 enhance the generation of PD-1-disrupted CTLs for adoptive immunotherapy

机译：用于共拖视增强的工程细胞联合IL-21增强了PD-1破坏了CTL的产生，用于采用免疫疗法

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摘要

Highlights ? Blockade of the immune cell checkpoint inhibitors programmed death 1 and programmed death-ligand 1 has become a powerful tool in cancer treatment. ? Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 modified cytotoxic T lymphocytes ranked superiorly in terms of immune responses and cytotoxicity. ? This study demonstrates that a genetically modified K562 cell line with surface expression of 4-1BB ligand combined with interleukin-21 enhance the generation of programmed death 1-disrupted cytotoxic T lymphocytes for adoptive immunotherapy. Abstract Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer. Our findings demonstrate that after a long-term, up to 28days, engineered cells for costimulatory enhancement (ECCE) combined with IL-21 promote the expansion of PD-1-disrupted CTLs with a less differentiated “young” phenotype, enhanced immune response and superior cytotoxic effector characteristics. These new in vitro conditions represent a nimble and cost-effective approach to developing PD-1-disrupted CTLs with improved therapeutic potential.
机译：强调 ？阻断免疫细胞检查点抑制剂编程死亡1和编程死亡 - 配体1已成为癌症治疗的强大工具。还我们以前的研究表明，通过减少免疫耐受性，通常在免疫应答和细胞毒性方面进行聚集的群体分类的短文重复相关蛋白质9改性细胞毒性T淋巴细胞。还本研究表明，具有4-1BB配体的表面表达的遗传修饰的K562细胞系与白细胞介素-21联合增强了用于采用免疫疗法的编程死亡1破坏细胞毒性T淋巴细胞的产生。摘要阻断免疫细胞检查点抑制剂编程死亡1（PD-1）和编程的死亡 - 配体1（PD-L1）已成为癌症治疗中的强大工具，这在各种固体癌症类型和血液学恶性肿瘤上有效。我们以前的研究表明，通过减少免疫耐受性，在免疫应答和细胞毒性方面，通过降低免疫耐受性的短语重复 - 相关蛋白9（CRISPR-CAS9）改性细胞毒性T淋巴细胞（CTL）。在该研究中，开发了一种具有4-1BBL表面表达的遗传修饰的K562细胞系，以在体外扩增PD-1破坏的CTL，以进一步采用免疫治疗免疫癌症。我们的研究结果表明，经过长期，高达28天的成本增强（ECCE）的工程细胞与IL-21相结合，促进了PD-1破坏的CTL的扩张，具有较差的“年轻”表型，增强的免疫应答和增强的免疫应答优异的细胞毒性效应器特性。这些新的体外条件代表了一种亮度和具有成本效益的方法，以改善治疗潜力的PD-1破坏的CTL。

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  • 来源
    《Cellular immunology》 |2017年第2017期|共8页
  • 作者

    Jie Shao; Qiuping Xu; Shu Su; Fanyan Meng; Zhengyun Zou; Fangjun Chen; Juan Du; Xiaoping Qian; Baorui Liu;

  • 作者单位

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

    The Comprehensive Cancer Center of Drum Tower Hospital Medical School of Nanjing University &

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Adoptive cell therapy; Checkpoint blockade; 4-1BB ligand; Interleukin-21; Clustered regularly interspaced short palindromic repeat;

    机译：采用细胞疗法;检查点封锁;4-1BB配体;白细胞介素-21;聚集经常间隙的短文重复;

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