Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells
Effective induction of anti-tumor immune responses with oligomannose-coated liposome targeting to intraperitoneal phagocytic cells
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DOI：
10.1016/j.canlet.2007.10.038
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发表时间：
2008-02-18
期刊：
影响因子：
9.7
通讯作者：
Kojima, Naoya
中科院分区：
文献类型：
--
作者：
Ikehara, Yuzuru;Shiuchi, Nobumitsu;Kojima, Naoya
我们最近建立了一种新的药物递送系统（DDS），其使用可能被巨噬细胞（M phi）摄取的低聚甘露糖包覆的脂质体（OML），以将抗癌药物携带到被称为胃癌优先转移部位的乳斑[Y.池原，T.尼瓦湖Biao，S.K. Ikehara，N. Ohashi，T.小林，Y. Shimizu，N. Kojima，H. Nakanishi，A carbohydrate preparation-based drug delivery and controlled release system using peritoneal macrophages as a cellular vehicle，Cancer Res.66（2006）8740-8748]。在本研究中，我们应用这种腹腔内DDS的全身性癌症免疫治疗采用卵清蛋白（OVA）作为模型抗原。吸收注射到腹膜腔中的含有FITC-OVA的OML的细胞主要是M（，因为它们显示出粘附特性并且几乎仅表达F4/80和CD 11b。吞噬细胞还直接摄取裸OVA至与OML-封闭的OVA（OML-OVA）相同的程度，因为它是高度甘露糖化的蛋白质。然而，摄取OML-OVA的吞噬细胞可以在体外比摄取裸OVA的吞噬细胞更有效地激活OVA特异性CD 8（+）（来自OT-I：H-2K（B）/OVA（257-264）特异性）和CD 4（+）（来自OT-II：H-2A（B）/OVA（323-339）特异性）T细胞。此外，仅用OML-OVA预免疫的小鼠排斥E.G7-OVA（OVA转染的EL 4），但不排斥EL 4。这些结果表明，OML也可以用作有效的抗原递送系统，用于激活CTL和Th亚群的癌症免疫治疗。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
We recently established a novel drug delivery system (DDS) using oligomannose-coated liposomes (OMLs) which are probably taken up by macrophages (M phi) to carry anti-cancer drugs to milky spots known as preferential metastatic sites of gastric cancers [Y. Ikehara, T. Niwa, L. Biao, S.K. Ikehara, N. Ohashi, T. Kobayashi, Y. Shimizu, N. Kojima, H. Nakanishi, A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle, Cancer Res. 66 (2006) 8740-8748]. In the present study, we applied this intraperitoneal DDS for systemic cancer immunotherapy employing ovalbumin (OVA) as a model antigen. The cells taking up the OMLs containing FITC-OVA injected into the peritoneal cavity were predominantly M(, as they showed adhesive characteristics and expressed F4/80 and CD11b almost exclusively. The phagocytic cells also took up bare OVA directly to the same extent as OML-enclosed OVA (OML-OVA), as it is a highly mannosilated protein. The phagocytic cells taking up OML-OVA, however, could activate OVA-specific CD8(+) (from OT-I: H-2K(b)/OVA(257-264)-specific)and CD4(+) (from OT-II: H-2A(b)/OVA(323-339)-specific) T cells much more effectively in vitro than those taking up bare OVA. Furthermore, only the mice pre-immunized with OML-OVA rejected E.G7-OVA (OVA-transfected EL4) but not EL4. These results indicate that the OMLs can also be used as an effective antigen delivery system for cancer immunotherapy activating both CTL and Th subsets. (C) 2007 Elsevier Ireland Ltd. All rights reserved.