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      生物資訊

      基因修飾T細(xì)胞可幫免疫系統(tǒng)攻擊腫瘤,為此被稱為腫瘤治療的"第五支柱"

      作者:admin 來源:Sci Transl Med 發(fā)布時(shí)間: 2014-11-25 09:01  瀏覽次數(shù):
      購(gòu)買進(jìn)口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.effectnews.cn

      細(xì)胞治療使用的 lonza 04-418Q 無血清培養(yǎng)基 (點(diǎn)擊標(biāo)題進(jìn)入)

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          基因修飾T細(xì)胞因可幫助人體免疫系統(tǒng)識(shí)別并攻擊腫瘤,為此被稱為腫瘤治療的"第五支柱"。

          上述治療方法已經(jīng)在血癌,如白血病中顯示出治療功效。在某些腫瘤類型如間皮瘤治療過程中,當(dāng)這些“修修補(bǔ)補(bǔ)”的T細(xì)胞被再注入到患者血液中時(shí),患者腫瘤會(huì)很好抵抗T細(xì)胞攻擊。

          研究人員試圖直接向腫瘤區(qū)域提供基因修飾后的T細(xì)胞,并發(fā)現(xiàn)這些T細(xì)胞不僅攻擊了癌細(xì)胞,同時(shí)成功阻斷了癌癥再次發(fā)生。他們的研究結(jié)果發(fā)表在Science Translational Medicine雜志上。

          該研究主要使用人源T細(xì)胞和小鼠腫瘤,其研究結(jié)果有助于加快開展1期臨床試驗(yàn)。研究人員嘗試了兩種靜脈注射,將重新裝備(基因修飾)的T細(xì)胞注射入間皮瘤小鼠胸膜腔。奇怪的是,當(dāng)基因修飾的T細(xì)胞到達(dá)腫瘤部位,它們能“看到”敵人(癌細(xì)胞),激活自己的同時(shí)也激活其他T細(xì)胞。

           十多年來,研究人員已經(jīng)嘗試了基因改變T細(xì)胞使其產(chǎn)生受體,以匹配腫瘤細(xì)胞的抗原。上個(gè)月,研究人員在費(fèi)城兒童醫(yī)院報(bào)道,當(dāng)患者的T細(xì)胞進(jìn)行基因修飾并重新引入患者體內(nèi)后,30名晚期復(fù)發(fā)的白血病患者中有27名患者經(jīng)歷緩解期。

      原文鏈接地址:

      http://news.bioon.com/article/6661953.html

       

       

      英文版

      Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity.

      Adusumilli PS,et al.

      Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intrapleurally administered CAR T cells vastly outperformed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions. After intrapleural T cell administration, prompt in vivo antigen-induced T cell activation allowed robust CAR T cell expansion and effector differentiation, resulting in enhanced antitumor efficacy and functional T cell persistence for 200 days. Regional T cell administration also promoted efficient elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent on early CD4(+) T cell activation associated with a higher intratumoral CD4/CD8 cell ratios and CD28-dependent CD4(+) T cell-mediated cytotoxicity. In contrast, intravenously delivered CAR T cells, even when accumulated at equivalent numbers in the pleural tumor, did not achieve comparable activation, tumor eradication, or persistence. The ability of intrapleurally administered T cells to circulate and persist supports the concept of delivering optimal CAR T cell therapy through "regional distribution centers." On the basis of these results, we are opening a phase 1 clinical trial to evaluate the safety of intrapleural administration of mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies.

       

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