CLINICAL TRIAL: CRETI-NH -- PHASE I STUDY OF CD19 CHIMERIC RECEPTOR EXPRESSING T

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 低级别淋巴瘤和慢性淋巴细胞性白血病(B-CLL)患者只要接受几年的最低限度治疗，就可以体验到良好的生活质量。然而，这种疾病总是会进展到对常规治疗产生抗药性。另一种方法是基于干细胞移植，因为捐赠者的免疫可以攻击肿瘤(移植物对淋巴瘤)。这种效应是由被称为T淋巴细胞的细胞产生的，T淋巴细胞是移植物的细胞成分之一。然而，这些细胞也可以攻击患者的正常器官，产生移植物抗宿主病，这可能是致命的。利用基因转移技术，有可能利用T淋巴细胞的肿瘤杀伤能力，同时避免它们对正常组织造成损害的能力。我们建议将患者自己的T细胞放入一种人造结构(受体)的基因中，这种结构将引导T淋巴细胞到达肿瘤并允许他们杀死它。这些所谓的嵌合抗原受体(CAR)可以通过添加第二种成分来进一步改变，这种成分有助于在T淋巴细胞看到癌症靶点时触发它。我们现在建议使用一种改良的病毒(Moloney逆转录病毒载体)将这种CAR的基因插入患者的T细胞中，并将细胞回馈给患者。我们会将T细胞与含有额外第二组分(CD28)的CAR进行比较，并将给定的细胞与没有额外部分的CAR进行比较。 转基因T淋巴细胞将通过中心线或直接注入静脉注入患者体内。患者将在诊所接受治疗，并将在输液后密切监测几个小时。我们会定期从外周血中采集血液样本。我们将寻找我们植入患者体内的细胞的安全性、持久性和功能。最终，我们希望获得证据，证明这些CAR-T细胞在对抗癌症方面是有效的。 G

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with low-grade lymphomas and Chronic Lymphocytic Leukemia (B-CLL) can experience a good quality of life with minimal treatment for several years. However the disease invariably progresses to become resistant to conventional treatment. Alternative approaches are based on stem cell transplantation, since the incoming immunity of the donor can attack the tumor (Graft versus lymphoma). This effect is produced by cells called T-lymphocytes that are one of the cellular components of the graft. However, these cells can also attack the normal organs of the patient to produce graft versus host disease which can be fatal. Using gene transfer technology, it maybe possible to take advantage of the tumor killing ability of the T-lymphocytes, whilst avoiding their capacity to cause damage to normal tissue. We propose taking the patients own T cells and putting into them a gene for an artificial structure (receptor) that will direct the T-lymphocytes to the tumor and allow them to kill it. These so-called chimeric antigen receptors (CAR) can be further changed by adding a second component that helps to trigger the T-lymphocytes once it sees the cancer target. We now propose to insert the genes for this CAR into patients T cells using a modified virus (Moloney retroviral vector) and giving the cells back to the patients. We will compare the T cells with the CAR containing the extra second component (CD28) with cells given a CAR that lacks this extra piece. The genetically modified T-lymphocytes will be infused into patients through a central line or directly into a vein. Patients will be treated in the clinic and will be monitored closely for several hours after infusion. We will collect samples of blood from peripheral blood at regular intervals. We will look for the safety, the persistence and the function of the cells we put into the patients. Ultimately we hope to get evidence that these CAR-T cells are effective at fighting the cancer. G