Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors.
Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors.
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DOI：
10.1038/nrclinonc.2013.46
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Rosenberg SA
中科院分区：
文献类型：
--
作者：
Kochenderfer JN;Rosenberg SA
大多数B细胞恶性肿瘤表达CD19，大多数B细胞恶性肿瘤患者无法通过目前的标准治疗方法治愈。嵌合抗原受体(CARS)是由抗原识别部分和T细胞激活区组成的融合蛋白。T细胞可以被转基因来表达CARS，抗CD19 CAR T细胞的过继转移现在正在进行临床试验。抗CD19 CAR T细胞的有效临床治疗于2010年首次报道，当时在NCI接受治疗的一名晚期淋巴瘤患者经历了淋巴瘤的部分缓解和正常B细胞的长期根除。更多的患者随后在注射抗CD19 CAR T细胞后获得了晚期B细胞恶性肿瘤的长期缓解。从接受抗CD19 CAR T细胞输注的患者中长期根除正常的CD19+B细胞证明了这些T细胞具有强大的抗原特异性活性。一些接受抗CD19CAR T细胞治疗的患者出现了急性不良反应，这与血清炎性细胞因子水平升高有关。尽管抗CD19 CAR T细胞仍处于早期发展阶段，但在患者中观察到的强大的抗原特异性活性表明，输注抗CD19 CAR T细胞可能成为一些B细胞恶性肿瘤的标准治疗方法。
Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a patient with advanced-stage lymphoma treated at the NCI experienced a partial remission of lymphoma and long-term eradication of normal B cells. Additional patients have subsequently obtained long-term remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR T cells. Long-term eradication of normal CD19+ B cells from patients receiving infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific activity of these T cells. Some patients treated with anti-CD19 CAR T cells have experienced acute adverse effects, which were associated with increased levels of serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early stage of development, the potent antigen-specific activity observed in patients suggests that infusions of anti-CD19 CAR T cells might become a standard therapy for some B-cell malignancies.
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DOI：
10.1097/cji.0b013e318194a6e8
发表时间：
2009-02
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Hollyman D;Stefanski J;Przybylowski M;Bartido S;Borquez-Ojeda O;Taylor C;Yeh R;Capacio V;Olszewska M;Hosey J;Sadelain M;Brentjens RJ;Rivière I
通讯作者：
Rivière I
通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
影响因子：
7
作者：
Brenner MK;Heslop HE
通讯作者：
Heslop HE
影响因子：
6.5
作者：
Cheadle, EJ;Gilham, DE;Hawkins, RE
通讯作者：
Hawkins, RE
影响因子：
20.3
作者：
Bacher, Ulrike;Klyuchnikov, Evgeny;Hari, Parameswaran N.
通讯作者：
Hari, Parameswaran N.