Dendritic Cells That Endocytosed Antigen-Containing IgG-Liposomes Elicit Effective Antitumor Immunity
Dendritic Cells That Endocytosed Antigen-Containing IgG-Liposomes Elicit Effective Antitumor Immunity
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DOI：
10.1097/01.cji.0000190169.61416.f5
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发表时间：
2006-03
影响因子：
3.9
通讯作者：
K. Kawamura;N. Kadowaki;R. Suzuki;S. Udagawa;S. Kasaoka;N. Utoguchi;T. Kitawaki;N. Sugimoto;N. Okada;K. Maruyama;T. Uchiyama
中科院分区：
文献类型：
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作者：
K. Kawamura;N. Kadowaki;R. Suzuki;S. Udagawa;S. Kasaoka;N. Utoguchi;T. Kitawaki;N. Sugimoto;N. Okada;K. Maruyama;T. Uchiyama
脂质体是一种很有前途的载体，可将外源性抗原递送至树突状细胞（DC）用于肿瘤免疫治疗。已显示靶向DC上的Fcγ受体的外源性抗原导致抗原衍生肽在主要组织相容性复合物（MHC）I类和II类分子上的有效呈递。在这项研究中，它被调查是否DCs，内吞的物理化学优化的含抗原的脂质体与IgG缀合有效地提出抗原的MHC I类和II类分子，并因此诱导强的抗肿瘤免疫应答。直径为200 nm但不连接聚乙二醇的IgG缀合的脂质体最有效地被DC内吞。通过CD32内吞含破伤风类毒素（TT）的IgG脂质体的人单核细胞衍生的DC比用含TT的裸脂质体或用可溶性TT脉冲的DC更强烈地刺激CD4+ T细胞。用内吞含有卵清蛋白（OVA）的IgG脂质体但不含OVA的裸脂质体或可溶性OVA的DC免疫小鼠完全阻止了表达OVA的淋巴瘤细胞的生长。重要的是，给予具有已建立的表达OVA的肿瘤的小鼠内吞含有OVA的IgG脂质体的DC强烈抑制肿瘤生长。本研究证明了IgG脂质体具有适合于将抗原递送至DC的物理化学性质，并为IgG脂质体用于使用DC的肿瘤免疫治疗铺平了道路。
Liposomes represent a promising vehicle to deliver exogenous antigens to dendritic cells (DCs) for tumor immunotherapy. Targeting exogenous antigens to Fcγ receptors on DCs has been shown to result in efficient presentation of antigen-derived peptides on major histocompatibility complex (MHC) class I and class II molecules. In this study, it was investigated whether DCs that endocytosed physicochemically optimized antigen-containing liposomes conjugated with IgG efficiently present antigens on MHC class I and class II molecules, and consequently induce strong antitumor immune responses. IgG-conjugated liposomes that were 200 nm in diameter without attaching polyethylene glycol were most efficiently endocytosed by DCs. Human monocyte-derived DCs that endocytosed tetanus toxoid (TT)-containing IgG liposomes via CD32 stimulated CD4+ T cells more strongly than DCs pulsed with TT-containing bare liposomes or with soluble TT. Immunization of mice with DCs that endocytosed ovalbumin (OVA)-containing IgG liposomes but not OVA-containing bare liposomes or soluble OVA completely prevented the growth of OVA-expressing lymphoma cells. Importantly, administration of DCs that endocytosed OVA-containing IgG liposomes to the mice with established OVA-expressing tumors strongly suppressed tumor growth. This study demonstrates an IgG liposome with physicochemical properties suitable for delivering antigens to DCs and paves the way to the application of IgG liposomes for tumor immunotherapy using DCs.