Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen.
Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen.
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DOI：
10.1182/asheducation-2012.1.143
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Curran KJ
中科院分区：
文献类型：
--
作者：
Brentjens RJ;Curran KJ
具有免疫活性的供体 T 细胞介导有益的移植物抗白血病 (GVL) 效应的能力首次在用于治疗血液恶性肿瘤的同种异体造血干细胞移植 (allo-HSCT) 中得到证实。不幸的是，除了慢性粒细胞白血病和 EBV 诱导的淋巴增殖性疾病外，同种异体 HSCT GVL 缺乏显着影响大多数其他血液恶性肿瘤疾病进展或复发的效力。使用过去的方法的 GVL 效应的不足在淋巴恶性肿瘤患者中尤其明显。然而，随着改进的基因转移技术的出现，转基因肿瘤特异性免疫效应器已将细胞免疫疗法扩展到淋巴恶性肿瘤。一种有希望的策略是引入编码人工受体（称为嵌合抗原受体（CAR））的基因，它可以改变免疫效应器的特异性和功能。针对 B 细胞特异性 CD19 抗原的 CAR 修饰 T 细胞在多项早期临床试验中显示出有希望的结果，支持对 B 细胞癌症患者的进一步研究。然而，临床试验设计和 CAR 结构的差异使得该技术的最佳应用的发现变得复杂。最近的临床前研究支持对 CAR 修饰的 T 细胞进行额外的基因修饰，以利用这种新型过继性细胞疗法实现最佳临床疗效。
The ability of immune-competent donor T cells to mediate a beneficial graft-versus-leukemia (GVL) effect was first identified in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematologic malignancies. Unfortunately, with the exception of chronic myelogenous leukemia and EBV-induced lymphoproliferative disease, allo-HSCT GVL lacks the potency to significantly affect disease progression or recurrence in most other hematologic malignancies. The inadequacy of a GVL effect using past approaches is particularly evident in patients with lymphoid malignancies. However, with the advent of improved gene transfer technology, genetically modified tumor-specific immune effectors have extended cellular immunotherapy to lymphoid malignancies. One promising strategy entails the introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs), which redirect the specificity and function of immune effectors. CAR-modified T cells targeted to the B cell–specific CD19 antigen have demonstrated promising results in multiple early clinical trials, supporting further investigation in patients with B-cell cancers. However, disparities in clinical trial design and CAR structure have complicated the discovery of the optimal application of this technology. Recent preclinical studies support additional genetic modifications of CAR-modified T cells to achieve optimal clinical efficacy using this novel adoptive cellular therapy.
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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
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影响因子：
20.3
作者：
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通讯作者：
Riddell, Stanley R.
根据靶细胞的基因表达和染色质构象，基因治疗患者中逆转录病毒载体的整合特征是细胞特异性的。
影响因子：
11.1
作者：
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Aiuti, Alessandro
DOI：
10.1016/s1470-2045(10)70127-3
发表时间：
2010-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Eapen M;Rocha V;Sanz G;Scaradavou A;Zhang MJ;Arcese W;Sirvent A;Champlin RE;Chao N;Gee AP;Isola L;Laughlin MJ;Marks DI;Nabhan S;Ruggeri A;Soiffer R;Horowitz MM;Gluckman E;Wagner JE;Center for International Blood and Marrow Transplant Research;Acute Leukemia Working Party Eurocord (the European Group for Blood Marrow Transplantation);National Cord Blood Program of the New York Blood Center
通讯作者：
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影响因子：
82.9
作者：
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