Ichii S, Imai Y, Irimura T
Department of Cancer Biology and Molecular Immunology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan.
J Leukoc Biol. 1997 Dec;62(6):761-70. doi: 10.1002/jlb.62.6.761.
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.
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。