Inhibition of peritoneal dissemination of tumor cells by single dosing of phosphodiester CpG oligonucleotide/cationic liposome complex
Inhibition of peritoneal dissemination of tumor cells by single dosing of phosphodiester CpG oligonucleotide/cationic liposome complex
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DOI：
10.1016/j.jconrel.2006.08.002
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发表时间：
2006-10-10
影响因子：
10.8
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Kuramoto, Yukari;Nishikawa, Makiya;Hashida, Mitsuru
非甲基化的CpG ODN具有诱导抗肿瘤免疫、抑制肿瘤转移的作用，但其稳定性和对抗原提呈细胞的递呈能力有待提高。在这项研究中，我们制定了一个CpG ODN复合物与阳离子脂质体（CpG ODN-lipoplex）和其抗肿瘤活性进行了评估，在腹腔播散模型的肿瘤细胞稳定标记萤火虫荧光素酶基因。与未治疗小鼠相比，单次腹腔内给予CpG ODN-lipoplex使肿瘤细胞数量大大减少至0.01%或更低，这可能与TNF-α和IL-12的产生增加有关。CpG ODN-lipoplex增加了荷瘤小鼠的存活时间，并且大多数长期存活者拒绝再攻击的肿瘤细胞。这些结果表明，单次给药的CpG ODN-脂质复合物在抑制腹膜播散和诱导持久的抗肿瘤免疫中是有效的。(c)2006 Elsevier B. V.保留所有权利。
Although unmethylated CpG dinucleotide-containing oligodeoxynucleotides (CpG ODN) are able to inhibit tumor metastasis through the induction of antitumor immunity, their stability and delivery to antigen presenting cells needs to be improved. In this study, we formulated a CpG ODN complex with cationic liposomes (CpG ODN-lipoplex) and its antitumor activity was evaluated in peritoneal dissemination models of tumor cells stably labeled with firefly luciferase gene. A single intraperitoneal administration of CpG ODN-lipoplex greatly reduced the number of tumor cells to 0.01% or lower compared with that detected in untreated mice, which may be associated with increased production of TNF-alpha and IL-12. CpG ODN-lipoplex increased the survival time of the tumor-bearing mice, and most long-term survivors rejected rechallenged tumor cells. These results indicate that a single dosing of CpG ODN-lipoplex is effective in inhibiting peritoneal dissemination and inducing long-lasting antitumor immunity. (c) 2006 Elsevier B.V. All rights reserved.