Generation of a novel dendritic-cell vaccine using melanoma and squamous cancer stem cells.

Generation of a novel dendritic-cell vaccine using melanoma and squamous cancer stem cells.
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使用黑色素瘤和鳞状癌干细胞生成新型的树突状疫苗。

DOI:
10.3791/50561
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发表时间:
2014-01-06
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
通讯作者:
Wicha MS
Wicha MS
中科院分区:
其他
文献类型:
--
作者:
Li Q;Lu L;Tao H;Xue C;Teitz-Tennenbaum S;Owen JH;Moyer JS;Prince ME;Chang AE;Wicha MS

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我们使用ALDEFLUOR/ALDH作为标记物,从与C57 BL/6小鼠同基因的小鼠黑色素瘤D5和与C3 H小鼠同基因的鳞状细胞癌SCC 7中鉴定了富含癌症干细胞(CSC)的群体,并使用细胞裂解物作为抗原来源来脉冲树突状细胞(DC),测试了它们的免疫原性。在两种模型中以及分别在肺转移环境和皮下肿瘤生长环境中,用ALDH高CSC裂解物脉冲的DC比用未分选的全肿瘤细胞裂解物的裂解物脉冲的DC诱导显著更高的保护性抗肿瘤免疫。这种现象是由于CSC疫苗诱导的体液以及细胞抗CSC反应。特别地,从经受CSC-DC疫苗的宿主分离的脾细胞产生比从经受未分选的肿瘤细胞裂解物脉冲DC疫苗的宿主分离的脾细胞显著更高量的IFNγ和GM-CSF。这些结果支持开发用于辅助环境中的临床使用的基于自体CSC的治疗性疫苗的努力。
We identified cancer stem cell (CSC)-enriched populations from murine melanoma D5 syngeneic to C57BL/6 mice and the squamous cancer SCC7 syngeneic to C3H mice using ALDEFLUOR/ALDH as a marker, and tested their immunogenicity using the cell lysate as a source of antigens to pulse dendritic cells (DCs). DCs pulsed with ALDHhigh CSC lysates induced significantly higher protective antitumor immunity than DCs pulsed with the lysates of unsorted whole tumor cell lysates in both models and in a lung metastasis setting and a s.c. tumor growth setting, respectively. This phenomenon was due to CSC vaccine-induced humoral as well as cellular anti-CSC responses. In particular, splenocytes isolated from the host subjected to CSC-DC vaccine produced significantly higher amount of IFNγ and GM-CSF than splenocytes isolated from the host subjected to unsorted tumor cell lysate pulsed-DC vaccine. These results support the efforts to develop an autologous CSC-based therapeutic vaccine for clinical use in an adjuvant setting.
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