Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
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DOI：
10.1007/s00109-006-0102-0
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发表时间：
2006-12
期刊：
影响因子：
--
通讯作者：
Cao X
中科院分区：
文献类型：
--
作者：
Dai S;Zhou X;Wang B;Wang Q;Fu Y;Chen T;Wan T;Yu Y;Cao X
树突状细胞（DC）来源的或肿瘤来源的外泌体是一群纳米尺寸的膜囊泡，其可以诱导特异性抗肿瘤免疫。然而，基于外泌体的肿瘤疫苗的免疫原性潜力和效率不足以在临床试验中达到治疗效果。在这篇文章中，我们研究了肿瘤细胞的IL-18基因修饰是否可以增加来自IL-18基因修饰的肿瘤细胞的外泌体的功效。我们用编码人IL-18的重组腺病毒（AdhIL-18）转染表达癌胚抗原（CEA）的肿瘤细胞，并从IL-18基因修饰的肿瘤细胞制备exosomes，Exo/IL-18。我们发现Exo/IL-18天然含有CEA和生物活性IL-18。此外，Exo-IL-18具有趋化DC和T细胞，促进PBMC的增殖和Th 1细胞因子释放，并促进DC的表型和功能成熟的能力。此外，Exo/IL-18脉冲的DC在体外非常有效地从HLA-A*0201 CEA+癌症患者的PBMC诱导HLA-A * 0201限制性CEA特异性CD 8 + CTL。在几乎所有这些实验中，Exo/IL-18显示出比常规制备的来源于没有IL-18基因修饰的亲本肿瘤细胞的外泌体更有效的功能。我们的研究结果表明，Exo/IL-18具有更强的诱导特异性抗肿瘤免疫的能力，并且我们的IL-18修饰exosomes的策略是开发基于exosomes的肿瘤疫苗的可行方法。
Dendritic cells (DC)-derived or tumor-derived exosomes are a population of nanometer sized membrane vesicles that can induce specific anti-tumor immunity. However, the immunogenic potential and efficiency of exosomes-based tumor vaccine are not satisfactory enough to achieve a curative effect in clinical trials. In this article we investigated whether IL-18 genetic modification of tumor cells can increase the efficacy of exosomes derived from IL-18 gene-modified tumor cells. We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells. We found that Exo/IL-18 naturally contain CEA and bioactive IL-18. Moreover, Exo-IL-18 are potent in chemoattracting DC and T cells, enhancing the proliferation and Th1 cytokine release of PBMC, and promoting the phenotypic and functional maturation of DC. Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8+ CTL from the PBMC of HLA-A*0201 CEA+ cancer patients in vitro. In almost all of these experiments, Exo/IL-18 show more potent functions than the conventionally prepared exosomes derived from parent tumor cells without IL-18 gene modification. Our findings suggest that Exo/IL-18 has more potent capability to induce specific anti-tumor immunity, and our strategy of IL-18 modification of exosomes is a feasible approach to develop exosomes-based tumor vaccines.
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影响因子：
7.4
作者：
Morse MA;Garst J;Osada T;Khan S;Hobeika A;Clay TM;Valente N;Shreeniwas R;Sutton MA;Delcayre A;Hsu DH;Le Pecq JB;Lyerly HK
通讯作者：
Lyerly HK
影响因子：
15.9
作者：
Coughlin, CM;Salhany, KE;Lee, WMF
通讯作者：
Lee, WMF
影响因子：
82.9
作者：
Rosenberg, SA;Yang, JC;White, DE
通讯作者：
White, DE
影响因子：
4.4
作者：
Liu, SX;Yu, YZ;Cao, XT
通讯作者：
Cao, XT
影响因子：
4.4
作者：
Komai-Koma, M;Gracie, JA;Liew, FY
通讯作者：
Liew, FY