A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use.

A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use.
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DOI:
10.4049/jimmunol.0902255
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发表时间:
2010-01-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Calderwood SK
Calderwood SK
中科院分区:
其他
文献类型:
--
作者:
Gong J;Zhang Y;Durfee J;Weng D;Liu C;Koido S;Song B;Apostolopoulos V;Calderwood SK

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在以前的研究中,我们已经表明,来源于树突状细胞(DC)与肿瘤细胞(HSP 70.PC-F)融合的HSP 70-肽复合物(HSP 70. PC)与来自肿瘤细胞的HSP 70. PC相比具有上级性质。PC-F在刺激DC成熟和诱导CTL方面更有效,能够提供对肿瘤细胞攻击的小鼠的保护。为了开发用于患者使用的基于HSP 70. PC的肿瘤疫苗的改进制剂,我们从与患者来源的卵巢癌或建立的人乳腺癌细胞融合的DC中提取HSP 70.PC-F,并检查它们作为肿瘤疫苗的性质。与来源于肿瘤细胞的HSP 70. PC诱导的T细胞相比,HSP 70. PC-F诱导的T细胞表达更高水平的IFN-γ并表现出增加的肿瘤细胞杀伤水平。增强的HSP 70.PC-F的免疫原性与改进的疫苗组成相关,包括增加的肿瘤抗原及其加工的中间体的含量,以及其他HSP如HSP 90和HSP 110的检测。因此,本研究提供了一种替代的方法来制备基于HSP的疫苗,使用DC/肿瘤融合技术和温和,快速分离HSP. PC。
In previous studies we have shown that HSP70-peptide complexes (HSP70.PC) derived from the fusion of dendritic cells (DC) to tumor cells (HSP70.PC-F) possess superior properties compared to HSP70.PC from tumor cells. HSP70.PC-F are more effective in stimulation of DC maturation and induction of CTL that are able to provide protection of mice against challenge with tumor cells. To develop an improved formulation of HSP70.PC-based tumor vaccine for patient use, we extracted HSP70.PC-F from DC fused to patient derived ovarian cancer or established human breast cancer cells and examined their properties as tumor vaccines. HSP70.PC-F induced T cells that express higher levels of IFN-γ and exhibit increased levels of killing of tumor cells compared to those induced by HSP70.PC derived from tumor cells. Enhanced immunogenicity of HSP70.PC-F was associated with improved composition of the vaccine including increased content of tumor antigens and their processed intermediates, and the detection of other HSPs such as HSP90 and HSP110. The present study has therefore provided an alternative approach to preparation of HSP-based vaccines using DC/tumor fusion technology and gentle and rapid isolation of HSP.PC.
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