T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia.
T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia.
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带有嵌合抗原受体的T细胞具有有效的抗肿瘤作用，可以在晚期白血病患者中建立记忆。
DOI：
10.1126/scitranslmed.3002842
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发表时间：
2011-08-10
影响因子：
17.1
通讯作者：
June CH
中科院分区：
文献类型：
--
作者：
Kalos M;Levine BL;Porter DL;Katz S;Grupp SA;Bagg A;June CH
使用T淋巴细胞的肿瘤免疫疗法，其可以识别和破坏恶性细胞，受到分离和扩增限于肿瘤相关抗原的T细胞的能力的限制。嵌合抗原受体（汽车）由连接至激活T细胞的结构域的抗体结合结构域组成，可以通过允许T细胞对细胞表面抗原作出应答来克服耐受性;然而，迄今为止，经工程改造以表达汽车的淋巴细胞在临床试验中已证明了最小的体内扩增和抗肿瘤作用。我们报告说，靶向CD 19并含有来自CD 137和T细胞受体β链的共刺激结构域的CAR T细胞在三名接受晚期慢性淋巴细胞白血病（CLL）治疗的患者中输注后具有有效的非交叉耐药临床活性。工程化的T细胞在体内扩增>1000倍，运输到骨髓，并继续以高水平表达功能性汽车至少6个月。靶向毒性的证据包括B细胞发育不全以及浆细胞数量减少和低丙种球蛋白血症。平均而言，计算每个输注的表达CAR的T细胞根除至少1000个CLL细胞。此外，三分之二的患者在血液和骨髓中表现出CD 19特异性免疫反应，并伴有完全缓解。此外，这些细胞的一部分作为记忆CAR+ T细胞持续存在并保留抗CD 19效应子功能，表明这种主要组织相容性复合物非依赖性方法有效治疗B细胞恶性肿瘤的潜力。
Tumor immunotherapy with T lymphocytes, which can recognize and destroy malignant cells, has been limited by the ability to isolate and expand T cells restricted to tumor-associated antigens. Chimeric antigen receptors (CARs) composed of antibody binding domains connected to domains that activate T cells could overcome tolerance by allowing T cells to respond to cell surface antigens; however, to date, lymphocytes engineered to express CARs have demonstrated minimal in vivo expansion and antitumor effects in clinical trials. We report that CAR T cells that target CD19 and contain a costimulatory domain from CD137 and the T cell receptor ζ chain have potent non–cross-resistant clinical activity after infusion in three of three patients treated with advanced chronic lymphocytic leukemia (CLL). The engineered T cells expanded >1000-fold in vivo, trafficked to bone marrow, and continued to express functional CARs at high levels for at least 6 months. Evidence for on-target toxicity included B cell aplasia as well as decreased numbers of plasma cells and hypogammaglobulinemia. On average, each infused CAR-expressing T cell was calculated to eradicate at least 1000 CLL cells. Furthermore, a CD19-specific immune response was demonstrated in the blood and bone marrow, accompanied by complete remission, in two of three patients. Moreover, a portion of these cells persisted as memory CAR+ T cells and retained anti-CD19 effector functionality, indicating the potential of this major histocompatibility complex–independent approach for the effective treatment of B cell malignancies.
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病毒特异性的T细胞设计为共表达肿瘤特异性受体：神经母细胞瘤个体中的持久性和抗肿瘤活性。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
11.5
作者：
Kershaw, Michael H.;Westwood, Jennifer A.;Hwu, Patrick
通讯作者：
Hwu, Patrick
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
56.9
作者：
Naldini, L;Blomer, U;Trono, D
通讯作者：
Trono, D
影响因子：
64.5
作者：
IRVING, BA;WEISS, A
通讯作者：
WEISS, A