Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials.
Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials.
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DOI：
10.1371/journal.pone.0057838
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cooper LJ
中科院分区：
文献类型：
--
作者：
Jena B;Maiti S;Huls H;Singh H;Lee DA;Champlin RE;Cooper LJ
针对CD19治疗B细胞恶性肿瘤的临床试验正在进行中，抗肿瘤反应令人鼓舞。大多数人输注基因修饰的T细胞来表达嵌合抗原受体(CAR)，该嵌合抗原受体(CAR)来自CD19特异性鼠单抗(mAb，克隆FMC63)的scFv区。我们描述了一种新的抗独特型单抗(MAb)，用于检测过继转移前后CD19特异性CAR+T细胞。用表达FMC63抗原识别结构域的细胞疫苗免疫制备了该鼠单抗。该单抗(克隆号136.20.1)的特异性被限制在CAR的scFv区域，通过抑制CD19+肿瘤靶标的CAR依赖性裂解而得到证实。此克隆可用于检测外周血单核细胞中CD19特异性CAR+T细胞，灵敏度为1：1,000。在临床环境中，mAb用于告知给药的CD19特异性T细胞的免疫表型和持久性。因此，我们的CD19特异性CAR单抗(克隆号136.20.1)将对实施CD19特异性CAR+T细胞治疗B系恶性肿瘤的研究人员有用。所描述的开发CAR特异性抗独特型单抗的方法学可以扩展到在基于CAR的过继T细胞治疗的背景下针对不同肿瘤相关抗原的其他基因治疗试验。
Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR+ T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19+ tumor targets. This clone can be used to detect CD19-specific CAR+ T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR+ T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy.
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影响因子：
11.2
作者：
Singh H;Figliola MJ;Dawson MJ;Huls H;Olivares S;Switzer K;Mi T;Maiti S;Kebriaei P;Lee DA;Champlin RE;Cooper LJ
通讯作者：
Cooper LJ
影响因子：
56.9
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
20.3
作者：
Rossig, C;Bollard, CM;Brenner, MK
通讯作者：
Brenner, MK
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：
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DOI：
10.1038/nri2635
发表时间：
2009-10
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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