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嵌合抗原受体(CAR)特异性单克隆抗体在临床试验中检测靶向CD19特异性T细胞

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发表于 2015-11-7 23:11:48 | 显示全部楼层 |阅读模式
Chimeric Antigen Receptor (CAR)-Specific Monoclonal Antibody to Detect CD19-Specific T Cells in Clinical Trials
Abstract:
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.
嵌合抗原受体(CAR)特异性单克隆抗体在临床试验中检测靶向CD19特异性T细胞
摘要:针对B淋巴细胞恶性肿瘤上CD19分子的临床试验正在进行中,以鼓舞抗肿瘤反应。大多数被输注的T细胞基本上被改造来表达一个嵌合抗原受体(CAR),它的特异性来自CD19特异性鼠单克隆抗体(mab,克隆号FMC63)的scFV片段。我们设计了一种新型的抗特异性抗体来检测过继治疗前和治疗后靶向CD19嵌合抗原受体T细胞。这种鼠源单克隆抗体由一种表达单克隆分子FMC63抗原可识别区域的细胞疫苗,通过免疫反应生产出来。这种单抗(克隆号136.20.1)的特异性局限于CARscFV片段,通过抑制以CAR为基础的靶向CD19肿瘤细胞的溶解来确证。这种单克隆抗体能够被用来检测外周血单核细胞中的CD-19特异性CAR-T细胞,敏感性达到11000。在临床设置中,这种单抗被用来检测宿主体内CD-19特异性CAR-T细胞的免疫表型和持续性。因此,我们的CD-19特异性靶向CAR的单克隆抗体(克隆号136.20.1)将会被用来检测CD19 CART细胞对B淋巴细胞肿瘤的有效性。这种通过开发一个抗CAR特异性的单克隆抗体的方法,可以扩展到靶向不同肿瘤的,以CAR为基础的过继T细胞治疗的其他基因治疗试验中。

Chimeric Antigen Receptor (CAR)-Specific Monoclonal Antibody to Detect CD19-Spec.pdf

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 楼主| 发表于 2015-11-8 22:20:55 | 显示全部楼层
爱康得生物医学技术(苏州)有限公司,专注免疫治疗。
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