Delivery of tumor associated antigens to antigen presenting cells using penetratin induces potent immune responses

被引:34
作者
Apostolopoulos, V [1 ]
Pouniotis, DS [1 ]
van Maanen, PJ [1 ]
Andriessen, RW [1 ]
Lodding, J [1 ]
Xing, PX [1 ]
McKenzie, IFC [1 ]
Loveland, BE [1 ]
Pietersz, GA [1 ]
机构
[1] Austin Res Inst, Heidelberg, Vic 3084, Australia
关键词
penetratim; Antennapedia; MUC1; membrane translocating peptide; Trojan;
D O I
10.1016/j.vaccine.2006.01.032
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytoplasmic delivery of proteins or CTL epitopes is crucial for the presentation of antigen for the generation of CTL. We previously described the use of the 16-amino acid peptide penetratin from the Drosophila Antennapedia domain (Int) to transport CTL epitopes into cells. Here we show that, Int, incorporating MUC1 CTL epitopes in tandem is able to facilitate their rapid uptake by macrophages and dendritic cells (DC) in an energy-dependent endocytic pathway. We also demonstrate for the first time that Int conjugated proteins are also able to be efficiently taken up by DC. Furthermore, C57BL/6 and HLA-A2 transgenic mice immunized with the Int-peptides or Int-proteins induce strong IFN-gamma secreting T cells and weak IgG1 antibodies. Immunized C57BL/6 mice were protected against the growth of a MUC1(+) tumor cell line. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3191 / 3202
页数:12
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