A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy
A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy
复制标题
DOI：
10.1016/j.jconrel.2008.10.015
复制
发表时间：
2009-02-10
影响因子：
10.8
通讯作者：
Maruyama, Kazuo
中科院分区：
文献类型：
--
作者：
Suzuki, Ryo;Oda, Yusuke;Maruyama, Kazuo
在基于树突状细胞（DC）的癌症免疫治疗中，DC呈递源自MHC I类上的肿瘤相关抗原的肽是重要的。并激活肿瘤特异性细胞毒性T淋巴细胞（CTL）。然而，MHC I类通常呈递在胞质溶胶中表达的内源性抗原。因此，我们开发了一种能够将外源性抗原直接递送到DC的胞质溶胶中的创新方法：即，MHC I类呈递途径。在这项研究中，我们研究了使用全氟丙烷气体包封脂质体（气泡脂质体，BLs）和超声（US）暴露对DC中MHC I类呈递水平的抗原递送的影响，以及使用这种抗原递送系统在基于DC的癌症免疫治疗中的可行性。用卵清蛋白（OVA）作为模型抗原、BL和US暴露处理DC。卵清蛋白直接进入胞质溶胶，但不通过内吞途径，卵清蛋白衍生的肽呈递在MHC I类分子上。该结果表明，外源性抗原在递送到胞质溶胶中时可被识别为内源性抗原。用经OVA、BL和US暴露处理的DC免疫有效诱导了OVA特异性CTL，并导致对E.G7-OVA肿瘤的完全排斥。这些数据表明，BL和US暴露的组合是基于DC的癌症免疫治疗中有前途的抗原递送系统。(C)2008 Elsevier B. V.保留所有权利。
In dendritic cell (DC)-based cancer immunotherapy, it is important that DCs present peptides derived from tumor-associated antigens on MHC class I. and activate tumor-specific cytotoxic T lymphocytes (CTLs). However, MHC class I generally present endogenous antigens expressed in the cytosol. We therefore developed an innovative approach capable of directly delivering exogenous antigens into the cytosol of DCs: i.e., a MHC class I-presenting pathway. In this study, we investigated the effect of antigen delivery using perfluoropropane gas-entrapping liposomes (Bubble liposomes, BLs) and ultrasound (US) exposure on MHC class I presentation levels in DCs, as well as the feasibility of using this antigen delivery system in DC-based cancer immunotherapy. DCs were treated with ovalbumin (OVA) as a model antigen, BLs and US exposure. OVA was directly delivered into the cytosol but not via the endocytosis pathway, and OVA-derived peptides were presented on MHC class I. This result indicates that exogenous antigens can be recognized as endogenous antigens when delivered into the cytosol. Immunization with DCs treated with OVA, BLs and US exposure efficiently induced OVA-specific CTLs and resulted in the complete rejection of E.G7-OVA tumors. These data indicate that the combination of BLs and US exposure is a promising antigen delivery system in DC-based cancer immunotherapy. (C) 2008 Elsevier B.V. All rights reserved.