2012年9月26日 電 /生物谷BIOON/ --近日,，新加坡生物工程與納米技術(shù)研究所開展的一項(xiàng)研究利用人類胚胎干細(xì)胞（胚胎干細(xì)胞）生成樹突狀細(xì)胞（DC）來刺激免疫系統(tǒng)來抗腫瘤，該新方法可能是一個(gè)更經(jīng)濟(jì)方式來生成抗癌癥的治療性疫苗,。
樹突狀細(xì)胞提呈刺激免疫應(yīng)答的抗原物質(zhì),，以刺激免疫系統(tǒng)的其他細(xì)胞消除致病細(xì)胞,。DCs的這種能力使得樹突狀細(xì)胞是疫苗在體內(nèi)的理想選擇作用靶細(xì)胞。因此,，F(xiàn)DA最近批準(zhǔn)了第一個(gè)以DC為基礎(chǔ)的疫苗,。然而，源自另一個(gè)個(gè)體的DC可能遭到接受者免疫系統(tǒng)的攻擊,。因此,，以DC為基礎(chǔ)的疫苗已采用從自身個(gè)體中獲得樹突狀細(xì)胞，但這費(fèi)用是昂貴的,，細(xì)胞的供應(yīng)是有限的,。
然而，該研究使用人類胚胎干細(xì)胞為樹突狀細(xì)胞的供應(yīng)源,，但是由于這些DCs仍然容易受到免疫系統(tǒng)的攻擊,，研究人員Zeng等利用自然殺傷T細(xì)胞（iNKT）來解決這一困難。自然殺傷T細(xì)胞可以附著在糖蛋白分子CD1D上刺激DCs活性,，從而使它們能夠被免受免疫系統(tǒng)的影響,。研究人員基因改造從胚胎干細(xì)胞中來源的DCs以產(chǎn)生額外的CD1D。在α-半乳糖苷（α-GC）存在的情況下,，CD1D細(xì)胞所產(chǎn)生的更大量的糖蛋白觸發(fā)iNKT細(xì)胞,。
隨后,，他們發(fā)現(xiàn)α-GC用于誘導(dǎo)抗腫瘤反應(yīng)并不是必須的。因?yàn)樵缙谘芯恳呀?jīng)表明人與小鼠來源的α-GC可能會(huì)導(dǎo)致iNKT的激活失控,。事實(shí)上,，研究人員發(fā)現(xiàn)，黑色素瘤抗原修飾的DC已經(jīng)足夠能使免疫T細(xì)胞對(duì)抗黑色素瘤細(xì)胞,。人類胚胎干細(xì)胞生成樹突狀細(xì)胞（DC）來誘導(dǎo)抗腫瘤免疫力的研究揭示了人類胚胎干細(xì)胞可以被用來當(dāng)做樹突狀細(xì)胞的一大來源,，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.
