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人工抗原呈递细胞在诱导抗原特异性细胞毒性 T 淋巴细胞方面优于树突状细胞。

Artificial antigen-presenting cells are superior to dendritic cells at inducing antigen-specific cytotoxic T lymphocytes.

机构信息

The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.

The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.

出版信息

Cell Immunol. 2018 Dec;334:78-86. doi: 10.1016/j.cellimm.2018.10.002. Epub 2018 Oct 23.

Abstract

Adoptive immunotherapy is a promising cancer treatment that entails infusion of immune cells manipulated to have antitumor specificity, in vitro. Antigen-specific cytotoxic T lymphocytes are the main executors of transformed cells during cancer immunotherapy. To induce antigen-specific cytotoxic T lymphocytes, we developed artificial antigen-presenting cells (aAPCs) by engineering K562 cells with electroporation to direct the stable expression of HLA-A∗0201, CD80, and 4-1BBL. Our findings demonstrate that after three stimulation cycles, the aAPCs promoted the induction of antigen-specific cytotoxic T lymphocytes with a less differentiated "young" phenotype, which enhanced immune responses with superior cytotoxicity. This novel, easy, and cost-effective approach to inducing antigen-specific cytotoxic T lymphocytes provides the possibility of improved cancer therapies.

摘要

过继免疫疗法是一种很有前途的癌症治疗方法,包括输注经过体外修饰以具有抗肿瘤特异性的免疫细胞。抗原特异性细胞毒性 T 淋巴细胞是癌症免疫治疗中靶向转化细胞的主要执行者。为了诱导抗原特异性细胞毒性 T 淋巴细胞,我们通过电穿孔工程化 K562 细胞来稳定表达 HLA-A∗0201、CD80 和 4-1BBL,从而开发了人工抗原呈递细胞(aAPC)。我们的研究结果表明,经过三个刺激周期后,aAPC 促进了具有较少分化“年轻”表型的抗原特异性细胞毒性 T 淋巴细胞的诱导,从而增强了具有更高细胞毒性的免疫反应。这种新颖、简单且具有成本效益的诱导抗原特异性细胞毒性 T 淋巴细胞的方法为改善癌症治疗提供了可能。

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