（圖片來源：Proceedings of the National Academy of Sciences）
近日一篇發(fā)表在美國(guó)國(guó)家科學(xué)院院刊（Proceedings of the National Academy of Sciences）的文章稱,，研究者通過基因工程技術(shù)研制出了可產(chǎn)生特異性抗腫瘤人類T淋巴細(xì)胞的小鼠模型，該模型或可成為人類腫瘤研究的重要方法,。
有研究證明經(jīng)基因修飾的T細(xì)胞受體（TCR）可識(shí)別并攻擊特定的腫瘤細(xì)胞,，但其過程較為復(fù)雜且無法產(chǎn)生穩(wěn)定并具有自我更新能力的T細(xì)胞。因此本文的研究者制造出了可在其體內(nèi)產(chǎn)生特異性抗黑素瘤的人類T淋巴細(xì)胞的小鼠模型,，該T細(xì)胞由經(jīng)過基因修飾的人類造血干細(xì)胞發(fā)展而來,。
此前有人制造了可產(chǎn)生HIV特異性T細(xì)胞模型，但由于該模型無法完全重建人類細(xì)胞而導(dǎo)致其結(jié)果無法在體內(nèi)進(jìn)行檢測(cè),。研究者于是對(duì)該模型進(jìn)行了改進(jìn),，他們通過將一個(gè)有功能的人類胸腺和經(jīng)黑素瘤特異性TCR轉(zhuǎn)導(dǎo)的人類造血祖細(xì)胞結(jié)合在一起修復(fù)了該缺陷,。
隨后研究者以黑素瘤為檢測(cè)對(duì)象進(jìn)行檢測(cè)，結(jié)果發(fā)現(xiàn)大多數(shù)小鼠體內(nèi)的腫瘤都得到了清除,，或者體積縮小,。而且，這些轉(zhuǎn)導(dǎo)的人類細(xì)胞在移植4個(gè)月后仍可以檢測(cè)到,，表明該干細(xì)胞的重建一旦啟動(dòng)便可長(zhǎng)期存在,。
該研究表明，將人類造血祖細(xì)胞使用基因工程的方法進(jìn)行修飾,，或許可以成為人類對(duì)抗慢性疾病如腫瘤的新武器,。（生物谷bioon.com）
doi:10.1073/pnas.1115050108
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PMID:
Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells
Dimitrios N. Vatakis, Richard C. Koya, Christopher C. Nixon,Liu Wei, Sohn G. Kim, Patricia Avancena, Gregory Bristol,David Baltimore, Donald B. Kohn , Antoni Ribas,Caius G. Radu, Zoran Galic, and Jerome A. Zack.
The goal of cancer immunotherapy is the generation of an effective, stable, and self-renewing antitumor T-cell population. One such approach involves the use of high-affinity cancer-specific T-cell receptors in gene-therapy protocols. Here, we present the generation of functional tumor-specific human T cells in vivo from genetically modified human hematopoietic stem cells (hHSC) using a human/mouse chimera model. Transduced hHSC expressing an HLA-A*0201-restricted melanoma-specific T-cell receptor were introduced into humanized mice, resulting in the generation of a sizeable melanoma-specific na?ve CD8+ T-cell population. Following tumor challenge, these transgenic CD8+ T cells, in the absence of additional manipulation, limited and cleared human melanoma tumors in vivo. Furthermore, the genetically enhanced T cells underwent proper thymic selection, because we did not observe any responses against non-HLA-matched tumors, and no killing of any kind occurred in the absence of a human thymus. Finally, the transduced hHSC established long-term bone marrow engraftment. These studies present a potential therapeutic approach and an important tool to understand better and to optimize the human immune response to melanoma and, potentially, to other types of cancer.
