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表达巨噬细胞凝集素的过继转移T细胞系的肿瘤部位选择性定位

Tumor site-selective localization of an adoptively transferred T cell line expressing a macrophage lectin.

作者信息

Ichii S, Imai Y, Irimura T

机构信息

Department of Cancer Biology and Molecular Immunology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan.

出版信息

J Leukoc Biol. 1997 Dec;62(6):761-70. doi: 10.1002/jlb.62.6.761.

DOI:10.1002/jlb.62.6.761
PMID:9400817
Abstract

CTLL-2 cells were transfected with an expression vector that contained cDNA of a mouse macrophage galactose/N-acetylgalactosamine-specific calcium-type lectin (MMGL) and a stable transfectant (CTL-ML) was established. These cells and mock transfectant cells (CTL-CEP) were labeled with a long-term fluorescent cell tracer, DiI. The labeled cells were intravenously injected into mice that contained established lung metastases produced by OV2944-HM-1 ovarian tumor cells. Analyses with fluorescence microscopy of a series of frozen lung sections from the recipient mice revealed that CTL-ML preferentially accumulated in the lung metastatic nodules, whereas CTL-CEP did not. Time course studies showed that the preferential accumulation was evident 3 days after adoptive transfer. We also found that OV2944-HM-1 cells bound peanut agglutinin and Vicia villosa agglutinin B4, whose sugar specificity overlaps with the specificity of MMGL. These results suggested that MMGL molecules expressed on CTLL-2 cells contributed to their selective trafficking or retention in tumor foci possibly through recognition of tumor-associated cell surface carbohydrate antigens. These results also suggested that MMGL could be used for the selective targeting of effector cells in adoptive immunotherapy.

摘要

用包含小鼠巨噬细胞半乳糖/N-乙酰半乳糖胺特异性钙型凝集素(MMGL)cDNA的表达载体转染CTLL-2细胞,并建立稳定转染子(CTL-ML)。这些细胞和空转染细胞(CTL-CEP)用长期荧光细胞示踪剂DiI标记。将标记的细胞静脉注射到含有由OV2944-HM-1卵巢肿瘤细胞产生的已建立肺转移灶的小鼠体内。对受体小鼠一系列冷冻肺切片进行荧光显微镜分析显示,CTL-ML优先聚集在肺转移结节中,而CTL-CEP则不然。时间进程研究表明,过继转移后3天,优先聚集明显。我们还发现,OV2944-HM-1细胞结合花生凝集素和野豌豆凝集素B4,其糖特异性与MMGL的特异性重叠。这些结果表明,CTLL-2细胞上表达的MMGL分子可能通过识别肿瘤相关细胞表面碳水化合物抗原,有助于其在肿瘤灶中的选择性运输或滞留。这些结果还表明,MMGL可用于过继免疫治疗中效应细胞的选择性靶向。

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引用本文的文献

1
Carbohydrate binding mechanism of the macrophage galactose-type C-type lectin 1 revealed by saturation transfer experiments.饱和转移实验揭示巨噬细胞半乳糖型C型凝集素1的碳水化合物结合机制
J Biol Chem. 2008 Nov 28;283(48):33665-73. doi: 10.1074/jbc.M804067200. Epub 2008 Sep 12.
2
Generation of mice deficient for macrophage galactose- and N-acetylgalactosamine-specific lectin: limited role in lymphoid and erythroid homeostasis and evidence for multiple lectins.巨噬细胞半乳糖和N - 乙酰半乳糖胺特异性凝集素缺陷小鼠的产生:在淋巴细胞和红细胞稳态中的作用有限及多种凝集素的证据
Mol Cell Biol. 2002 Jul;22(14):5173-81. doi: 10.1128/MCB.22.14.5173-5181.2002.