Pluripotent stem cells as source of dendritic cells for immune therapy
Pluripotent stem cells as source of dendritic cells for immune therapy
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DOI：
10.1007/s12185-010-0520-1
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发表时间：
2010-02
影响因子：
2.1
通讯作者：
S. Senju;S. Hirata;Yutaka Motomura;D. Fukuma;Y. Matsunaga;S. Fukushima;H. Matsuyoshi;Y. Nishimura
中科院分区：
文献类型：
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作者：
S. Senju;S. Hirata;Yutaka Motomura;D. Fukuma;Y. Matsunaga;S. Fukushima;H. Matsuyoshi;Y. Nishimura
树突状细胞（DC）是最有效的抗原呈递细胞。已证明携带抗原的 DC 的体内转移可有效引发针对抗原的 T 细胞反应。基于DC的细胞疫苗接种现在被认为是免疫治疗的有力手段，特别是抗癌免疫治疗。目前，许多机构都在进行用肽抗原脉冲或经过基因改造以呈递抗原的 DC 治疗的临床试验。此外，DC对免疫反应的抗原特异性负调节被认为是治疗自身免疫性疾病以及移植医学中引起移植物排斥和GVHD的同种异体反应性免疫反应的有前途的方法。用于转移治疗的DC现在是通过患者外周血单核细胞的体外分化产生的。然而，可用单核细胞的数量有限，并且单核细胞的 DC 分化潜力根据献血者的不同而变化。胚胎干（ES）细胞具有多能性和无限增殖能力。我们认为 ES 细胞是用于免疫治疗的 DC 的理想来源。包括我们在内的几个团队已经开发出了从 ES 细胞产生 DC 的方法。本综述介绍了源自 ES 细胞或诱导多能干 (iPS) 细胞的 DC 的产生、表征和遗传修饰的研究。还将讨论多能干细胞来源的DC临床应用之前需要解决的问题。
Dendritic cells (DC) are the most potent antigen-presenting cells. In vivo transfer of antigen-bearing DC has proven efficient in priming T cell responses specific to the antigen. DC-based cellular vaccination is now regarded as a powerful means for immunotherapy, especially for anti-cancer immunotherapy. Clinical trials of therapy with DC pulsed with peptide antigens or genetically modified to present antigens are currently carried out in many institutions. In addition, antigen-specific negative regulation of immune response by DC is considered to be a promising approach for treatments of autoimmune diseases and also for regulation of allo-reactive immune response causing graft rejection and GVHD in transplantation medicine. DC for transfer therapy are now generated by in vitro differentiation of peripheral blood monocytes of the patients. However, there is a limitation in the number of available monocytes, and the DC-differentiation potential of monocytes varies depending on the blood donor. Embryonic stem (ES) cells possess both pluripotency and infinite propagation capacity. We consider ES cells to be an ideal source for DC to be used in immunotherapy. Several groups, including us, have developed methods to generate DC from ES cells. This review introduces the studies on generation, characterization, and genetic modification of DC derived from ES cells or induced pluripotent stem (iPS) cells. The issues to be resolved before clinical application of pluripotent stem cell-derived DC will also be discussed.