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活化并扩增的自然杀伤细胞和T淋巴细胞对结直肠癌患者的疗效。

Efficacy of activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients.

作者信息

Subramani Baskar, Pullai Chithra Ramanathan, Krishnan Kohila, Sugadan Sheela Devi, Deng Xuewen, Hiroshi Terunuma, Ratnavelu Kananathan

机构信息

Nichi-Asia Life Science, Sdn. Bhd., Petaling Jaya 47810, Malaysia.

Biotherapy Institute of Japan, Tokyo 135-0051, Japan.

出版信息

Biomed Rep. 2014 Jul;2(4):505-508. doi: 10.3892/br.2014.264. Epub 2014 Mar 26.

DOI:10.3892/br.2014.264
PMID:24944796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4051481/
Abstract

Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced-toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the activation and expansion of NK and T cells was performed in Good Manufacturing Practice-certified clean rooms for ~12-15 days. Immunophenotypic analysis of the peripheral blood mononuclear cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and the patients were followed up. On average, 4.8×10 initial PBMCs and 2.7×10 total expanded cells were obtained. The intravenous infusions of the expanded cells were not accompanied by adverse reactions. Improved prognosis, reflected by a considerable decrease in the cancer markers, accompanied by an improved quality of life in the patients were observed. In conclusion, potential strategies are currently under development for the large-scale production of effectors cells; therefore, autologous immune enhancement therapy (AIET) may be considered as a viable approach to cancer treatment.

摘要

使用自然杀伤(NK)细胞和细胞毒性T细胞的基于免疫细胞的疗法一直受到密切关注,目的是设计一种有效且毒性降低的疗法,通过改善生活质量和预后使患者受益。分别对4例IV期结肠癌患者进行了1、3、5和6次效应细胞静脉输注。从患者采集外周血,并在符合药品生产质量管理规范(GMP)认证的洁净室中对NK和T细胞进行激活和扩增约12 - 15天。使用流式细胞术对外周血单个核细胞(PBMC)以及扩增后的NK和T细胞进行免疫表型分析,并对患者进行随访。平均获得4.8×10个初始PBMC和2.7×10个总扩增细胞。扩增细胞的静脉输注未伴随不良反应。观察到癌症标志物显著下降反映出预后改善,同时患者生活质量也得到改善。总之,目前正在开发用于大规模生产效应细胞的潜在策略;因此,自体免疫增强疗法(AIET)可被视为一种可行的癌症治疗方法。

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本文引用的文献

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Multi-modality treatment of colorectal liver metastases.结直肠癌肝转移的多模态治疗。
World J Gastroenterol. 2012 Jan 7;18(1):16-24. doi: 10.3748/wjg.v18.i1.16.
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Cytokine induced killer cells as promising immunotherapy for solid tumors.细胞因子诱导的杀伤细胞作为实体瘤有前途的免疫疗法。
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Ex vivo expansion of CD56+ NK and NKT-like lymphocytes from peripheral blood mononuclear cells of patients with ovarian neoplasia.从卵巢肿瘤患者外周血单个核细胞中体外扩增 CD56+NK 和 NKT-样淋巴细胞。
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In vitro stimulation and expansion of human tumour-reactive CD8+ cytotoxic T lymphocytes by anti-CD3/CD28/CD137 magnetic beads.采用抗 CD3/CD28/CD137 磁珠体外刺激和扩增人肿瘤反应性 CD8+细胞毒性 T 淋巴细胞。
Scand J Immunol. 2011 Aug;74(2):155-64. doi: 10.1111/j.1365-3083.2011.02564.x.
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NK cell-based immunotherapy for treating cancer: will it be promising?基于自然杀伤细胞的癌症免疫疗法:它会有前景吗?
Korean J Hematol. 2011 Mar;46(1):3-5. doi: 10.5045/kjh.2011.46.1.3. Epub 2011 Mar 15.
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Management of stage IV rectal cancer: palliative options.IV 期直肠癌的治疗:姑息治疗选择。
World J Gastroenterol. 2011 Feb 21;17(7):835-47. doi: 10.3748/wjg.v17.i7.835.
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Expansion, purification, and functional assessment of human peripheral blood NK cells.人外周血自然杀伤细胞的扩增、纯化及功能评估。
J Vis Exp. 2011 Feb 2(48):2540. doi: 10.3791/2540.
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Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review.主动特异性免疫治疗晚期结直肠癌和疑似结直肠微小残留病灶的临床疗效:荟萃分析和系统评价。
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Immunotherapy targeting colon cancer stem cells.针对结肠癌干细胞的免疫疗法。
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