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基因修饰T细胞可帮免疫系统攻击肿瘤,为此被称为肿瘤治疗的"第五支柱"

作者:admin 来源:Sci Transl Med 发布时间: 2014-11-25 09:01  浏览次数:
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细胞治疗使用的 lonza 04-418Q 无血清培养基 (点击标题进入)

干细胞治疗使用的 lonza 12-725F 无血清培养基 (点击标题进入)

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    基因修饰T细胞因可帮助人体免疫系统识别并攻击肿瘤,为此被称为肿瘤治疗的"第五支柱"。

    上述治疗方法已经在血癌,如白血病中显示出治疗功效。在某些肿瘤类型如间皮瘤治疗过程中,当这些“修修补补”的T细胞被再注入到患者血液中时,患者肿瘤会很好抵抗T细胞攻击。

    研究人员试图直接向肿瘤区域提供基因修饰后的T细胞,并发现这些T细胞不仅攻击了癌细胞,同时成功阻断了癌症再次发生。他们的研究结果发表在Science Translational Medicine杂志上。

    该研究主要使用人源T细胞和小鼠肿瘤,其研究结果有助于加快开展1期临床试验。研究人员尝试了两种静脉注射,将重新装备(基因修饰)的T细胞注射入间皮瘤小鼠胸膜腔。奇怪的是,当基因修饰的T细胞到达肿瘤部位,它们能“看到”敌人(癌细胞),激活自己的同时也激活其他T细胞。

     十多年来,研究人员已经尝试了基因改变T细胞使其产生受体,以匹配肿瘤细胞的抗原。上个月,研究人员在费城儿童医院报道,当患者的T细胞进行基因修饰并重新引入患者体内后,30名晚期复发的白血病患者中有27名患者经历缓解期。

原文链接地址:

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.

 

细胞治疗使用的 lonza 04-418Q 无血清培养基 (点击标题进入)

 
干细胞治疗使用的 lonza 12-725F 无血清培养基 (点击标题进入)
 
lonza 无血清培养基   (点击标题进入)

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