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

临床试验：CRETI-NH——CD19 嵌合受体表达的 I 期研究

• 批准号: 8356703
• 负责人: MALCOLM K. BRENNER
• 金额: $ 1.54万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356703
• 关键词: Antigen Receptors; Back; Blood specimen; CD19 gene; CD28 gene; Cell physiology; Cells; Chronic Lymphocytic Leukemia; Clinic; Clinical Research; Clinical Trials; Disease; Funding; Gene Transfer; Graft-Versus-Tumor Induction; Grant; Hour; Immunity; Infusion procedures; Lymphoma; Malignant Neoplasms; Moloney Leukemia Virus; Monitor; National Center for Research Resources; Normal tissue morphology; Organ; Patients; Principal Investigator; Quality of life; Research; Research Infrastructure; Resistance; Resources; Retroviral Vector; Safety; Source; Stem cell transplant; Structure; Synthetic Genes; T-Cell Receptor; T-Lymphocyte; Technology; United States National Institutes of Health; Veins; base; chimeric gene; conventional therapy; cost; experience; fighting; graft vs host disease; killings; peripheral blood; phase 1 study; receptor; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT 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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 摘要 低级别淋巴瘤和慢性淋巴细胞白血病（B-CLL）患者可以体验良好的生活质量，只需几年的最低限度治疗。 然而，这种疾病总是进展到对常规治疗产生耐药性。 替代方法是基于干细胞移植，因为供体的免疫力可以攻击肿瘤（移植物抗淋巴瘤）。 这种效应是由T淋巴细胞产生的，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。 使用基因转移技术，可以利用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。 我们建议提取患者自身的T细胞，并将一种人工结构（受体）的基因植入其中，这种结构将引导T淋巴细胞到达肿瘤并使其杀死肿瘤。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，一旦T淋巴细胞看到癌症靶点，这种成分有助于触发T淋巴细胞。 我们现在建议使用修饰的病毒（Moloney逆转录病毒载体）将这种CAR的基因插入患者的T细胞中，并将细胞返还给患者。 我们将比较具有含有额外第二组分（CD 28）的CAR的T细胞与给予缺乏该额外片段的CAR的细胞。 转基因T淋巴细胞将通过中心静脉或直接注入患者体内。 患者将在诊所接受治疗，并在输注后数小时内密切监测。 我们将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，我们希望得到证据证明这些CAR-T细胞能有效对抗癌症。