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

临床试验：CRETI-NH——表达 T 的 CD19 嵌合受体的 I 期研究

• 批准号: 8166724
• 负责人: MALCOLM K. BRENNER
• 金额: $ 0.5万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166724
• 关键词: Antigen Receptors; Back; Blood specimen; CD19 gene; Cell physiology; Cells; Chronic Lymphocytic Leukemia; Clinic; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Gene Transfer; Graft-Versus-Tumor Induction; Grant; Hour; Immunity; Infusion procedures; Institution; Lymphoma; Malignant Neoplasms; Moloney Leukemia Virus; Monitor; Normal tissue morphology; Organ; Patients; Phase; Quality of life; Research; Research Personnel; 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; experience; fighting; graft vs host disease; killings; peripheral blood; receptor; tumor; Antigen Receptors; Back; Blood specimen; CD19 gene; Cell physiology; Cells; Chronic Lymphocytic Leukemia; Clinic; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Gene Transfer; Graft-Versus-Tumor Induction; Grant; Hour; Immunity; Infusion procedures; Institution; Lymphoma; Malignant Neoplasms; Moloney Leukemia Virus; Monitor; Normal tissue morphology; Organ; Patients; Phase; Quality of life; Research; Research Personnel; 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; experience; fighting; graft vs host disease; killings; peripheral blood; receptor; tumor

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

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 低度淋巴瘤和慢性淋巴细胞性白血病（B-CLL）的患者可以通过最少的治疗经历良好的生活质量。 然而，该疾病总是会发展为抗传统治疗的能力。 替代方法是基于干细胞移植的，因为供体的传入免疫力可以攻击肿瘤（移植物与淋巴瘤）。 这种作用是由称为T淋巴细胞的细胞产生的，该细胞是移植物的细胞成分之一。 但是，这些细胞还可以攻击患者的正常器官，以产生与宿主疾病相比，这可能是致命的。 使用基因转移技术，也许可以利用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。 我们提议将患者自己的T细胞带入其中，将其放入人工结构（受体）的基因，该基因将T-淋巴细胞引导到肿瘤，并允许它们杀死它。 这些所谓的嵌合抗原受体（CAR）可以通过添加第二个成分一旦看到癌症靶标就可以触发T淋巴细胞，从而进一步更改。 现在，我们建议使用改良的病毒（Moloney逆转录病毒载体）将该汽车的基因插入患者T细胞中，并将细胞归还给患者。 我们将将T细胞与包含额外的第二个组件（CD28）的汽车与缺少此额外零件的汽车进行比较。 转基因的T淋巴细胞将通过中央线或直接静脉注入患者。 患者将在诊所接受治疗，并在输注后几个小时对患者进行治疗。 我们将定期从外周血中收集血液样本。 我们将寻找我们投入患者细胞的安全性，持久性和功能。 最终，我们希望获得证据表明这些CAR-T细胞有效地与癌症作斗争。 g