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生物資訊

基因修飾T細胞可幫免疫系統攻擊腫瘤,為此被稱為腫瘤治療的"第五支柱"

作者:admin 來源:Sci Transl Med 發布時間: 2014-11-25 09:01  瀏覽次數:
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    基因修飾T細胞因可幫助人體免疫系統識別并攻擊腫瘤,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,當這些“修修補補”的T細胞被再注入到患者血液中時,患者腫瘤會很好抵抗T細胞攻擊。

    研究人員試圖直接向腫瘤區域提供基因修飾后的T細胞,并發現這些T細胞不僅攻擊了癌細胞,同時成功阻斷了癌癥再次發生。他們的研究結果發表在Science Translational Medicine雜志上。

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

     十多年來,研究人員已經嘗試了基因改變T細胞使其產生受體,以匹配腫瘤細胞的抗原。上個月,研究人員在費城兒童醫院報道,當患者的T細胞進行基因修飾并重新引入患者體內后,30名晚期復發的白血病患者中有27名患者經歷緩解期。

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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干細胞治療使用的 lonza 12-725F 無血清培養基 (點擊標題進入)
 
lonza 無血清培養基   (點擊標題進入)

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