2012年9月26日 电 /生物谷BIOON/ --近日，新加坡生物工程与纳米技术研究所开展的一项研究利用人类胚胎干细胞（胚胎干细胞）生成树突状细胞（DC）来刺激免疫系统来抗肿瘤，该新方法可能是一个更经济方式来生成抗癌症的治疗性疫苗。
树突状细胞提呈刺激免疫应答的抗原物质，以刺激免疫系统的其他细胞消除致病细胞。DCs的这种能力使得树突状细胞是疫苗在体内的理想选择作用靶细胞。因此，FDA最近批准了第一个以DC为基础的疫苗。然而，源自另一个个体的DC可能遭到接受者免疫系统的攻击。因此，以DC为基础的疫苗已采用从自身个体中获得树突状细胞，但这费用是昂贵的，细胞的供应是有限的。
然而，该研究使用人类胚胎干细胞为树突状细胞的供应源，但是由于这些DCs仍然容易受到免疫系统的攻击，研究人员Zeng等利用自然杀伤T细胞（iNKT）来解决这一困难。自然杀伤T细胞可以附着在糖蛋白分子CD1D上刺激DCs活性，从而使它们能够被免受免疫系统的影响。研究人员基因改造从胚胎干细胞中来源的DCs以产生额外的CD1D。在α-半乳糖苷（α-GC）存在的情况下，CD1D细胞所产生的更大量的糖蛋白触发iNKT细胞。
随后，他们发现α-GC用于诱导抗肿瘤反应并不是必须的。因为早期研究已经表明人与小鼠来源的α-GC可能会导致iNKT的激活失控。事实上，研究人员发现，黑色素瘤抗原修饰的DC已经足够能使免疫T细胞对抗黑色素瘤细胞。人类胚胎干细胞生成树突状细胞（DC）来诱导抗肿瘤免疫力的研究揭示了人类胚胎干细胞可以被用来当做树突状细胞的一大来源，以生成DC疫苗。（生物谷：Bioon.com）
doi:10.4049/jimmunol.1102343
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Enhancing Immunostimulatory Function of Human Embryonic Stem Cell-Derived Dendritic Cells by CD1d Overexpression
Jieming Zeng*, Mohammad Shahbazi*, Chunxiao Wu*, Han Chong Toh and Shu Wang*,et al.
Human embryonic stem cell-derived dendritic cells (hESC-DCs) may potentially provide a platform to generate “off-the-shelf” therapeutic cancer vaccines. To apply hESC-DCs for cancer immunotherapy in a semiallogeneic setting, it is crucial for these cells to “jump-start” adaptive antitumor immunity before their elimination by host alloreaction. In this study, we investigated whether CD1d upregulation in hESC-DCs may exploit invariant NKT (iNKT) cell adjuvant activity and boost antitumor immunity. Using a baculoviral vector carrying the CD1d gene, we produced CD1d-overexpressing hESC-DCs and demonstrated that the upregulated CD1d was functional in presenting α-galactosylceramide for iNKT cell expansion. Pulsed with melanoma Ag recognized by T cell 1 peptide, the CD1d-overexpressing hESC-DCs displayed enhanced capability to prime CD8+ T cells without relying on α-galactosylceramide loading. Blocking the CD1d with Ab reduced the immunogenicity, suggesting the importance of hESC–DC and iNKT cell interaction in this context. The CD1d-overexpressing hESC-DCs also induced a proinflammatory cytokine profile that may favor the T cell priming. Moreover, a similar immunostimulatory effect was observed when the CD1d upregulation strategy was applied in human monocyte-derived dendritic cells. Therefore, our study suggests that the upregulation of CD1d in hESC-DCs provides a novel strategy to enhance their immunogenicity. This approach holds potential for advancing the application of hESC-DCs into human cancer immunotherapy.
