Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines.

Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines.
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慢病毒载体介导的小鼠骨髓细胞自主分化为免疫有效的树突状细胞疫苗。

DOI:
10.1038/mt.sj.6300126
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发表时间:
2007
期刊:
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子:
--
通讯作者:
Stripecke,Renata
Stripecke,Renata
中科院分区:
--
文献类型:
--
作者:
Koya,RichardC;Kimura,Takahiro;Ribas,Antoni;Rozengurt,Nora;Lawson,GregoryW;Faure-Kumar,Emmanuelle;Wang,He-jing;Herschman,Harvey;Kasahara,Noriyuki;Stripecke,Renata

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促进生成用于临床试验的树突状细胞(DC)疫苗并提高其生存能力、生物分布和刺激抗原特异性免疫反应的能力的方法对免疫治疗至关重要。我们用慢病毒载体(LV-GI4)对小鼠骨髓(BM)细胞进行编程,使它们能够自主产生粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4 (IL-4)。DC/LV-GI4细胞通过自主反分化产生典型的DC表型特征。DC/LV-GI4细胞在体内或体内自我分化,显示出持久和强大的活力,并刺激DC大量流入引流淋巴结(LNs)。采用MART1和TRP2共表达黑色素瘤抗原,评价DC/LV-GI4细胞的免疫刺激作用。注射DC/LV-GI4细胞的小鼠产生了有效的针对黑色素瘤的抗原特异性反应,这与保护性和长期治疗性抗肿瘤作用相关。因此,DC前体可以在单次免疫操作后进行基因工程改造,从而提高DC疫苗的活性。
See page 846Approaches facilitating generation of dendritic cell (DC) vaccines for clinical trials and enhancing their viability, bio-distribution, and capacity to stimulate antigen-specific immune responses are critical for immunotherapy. We programmed mouse bone marrow (BM) cells with lentiviral vectors (LV-GI4) so that they produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in an autonomous manner. DC/LV-GI4 cells underwent autonomous trans-differentiation to yield typical phenotypic characteristics of DCs. DC/LV-GI4 cells that self-differentiated eitherex vivoorin vivoshowed persistent and robust viability and stimulated high influx of DCs into draining lymph nodes (LNs). The immunostimulatory efficacy of DC/LV-GI4 cells was evaluated using MART1 and TRP2 as co-expressed melanoma antigens. Mice vaccinated with DC/LV-GI4 cells that self-differentiatedin vitroorin vivoproduced potent antigen-specific responses against melanoma, which correlated with protective and long-term therapeutic anti-tumor effects. Thus, DC precursors can be genetically engineered after a singleex vivomanipulation, resulting in DC vaccines with improved activity.
白血病细胞疫苗联合表达 CD80 和粒细胞-巨噬细胞集落刺激因子:在模拟费城染色体阳性急性淋巴细胞白血病的小鼠模型中进行临床前研究。
DOI: 10.1089/10430349950017103
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影响因子: 11.2
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发表时间: 2000
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影响因子: --
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