MOST CLOSELY HLA MATCHED ALLOGENEIC VIRUS SPECIFIC CYTOTOXIC T-LYMPHOCYTES (CTL)

HLA 最接近匹配的同种异体病毒特异性细胞毒性 T 淋巴细胞 (CTL)

• 批准号: 8166725
• 负责人: HELEN E HESLOP
• 金额: $ 0.42万
• 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/8166725
• 关键词: Adenovirus Infections; Adenoviruses; Allogenic; Antiviral Agents; Back; Blood Cells; Blood donor; Cell Line; Cells; Complication; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Disabled Persons; Donor person; Freezing; Funding; Genes; Genetic; Grant; Hematological Disease; Hematopoietic Neoplasms; Human Herpesvirus 4; Immune; Immune system; Infection; Infusion procedures; Institution; Laboratories; Lymphocyte; Monitor; Patients; Research; Research Personnel; Resources; Risk; Safety; Source; Stem cell transplant; T-Lymphocyte; Testing; Transplant Recipients; Transplantation; United States National Institutes of Health; Viral; Virus; Virus Diseases; cell killing; cytotoxic; graft vs host disease; monocyte; prevent; vector

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. When patients undergo a hemopoietic stem cell transplant (HSCT) from a donor who is the best possible match to treat blood cancers or other blood diseases they have a risk of infection until they can grow a new immune system from the donor. During this period they may develop serious viral infections with Epstein Barr virus (EBV), cytomegalovirus and adenovirus being three of the most common viruses that can cause problems. Investigators have previously shown that it is possible to grow up special T cells called virus-specific CTLs from the transplant donor that can prevent and treat these viral infections when they are given back to the patient. However it takes 2-3 months to grow these cells so it is not a practical option to grow virus-specific CTLs from the transplant donor for every patient that gets an infection with one of these viruses. In this study, investigators will see if an alternative approach is to make banks of virus-specific CTLs from normal donors that could be stored frozen and then made available to treat subjects post transplant if they developed one of these viral infections. Virus-specific CTL lines will be grown from normal donors and frozen. To make the CTL lines we first infect blood cells called monocytes with a specially produced adenovirus (a vector) that also carries part of the Cytomegalovirus (CMV) gene. This is a disabled virus that cannot reproduce itself once infection has occurred so it cannot spread. These infected monocytes then stimulate the T cells to respond to adenoviruses and CMV, and kill the cells infected with these viruses. We then give a second stimulation to the T cells, using cells which are also infected with EBV (which we will make from donor blood by infecting them with EBV in the laboratory) so that the cells now recognize three viruses CMV, EBV and Adenovirus. Once we have made sufficient numbers of T cells we will test them to make sure they kill cells infected with these viruses and freeze them. If a transplant patient gets an infection with one of these viruses, and the infection persists despite standard therapy, he or she would be eligible to receive a suitably matched CTL line. The primary objective is to determine if this strategy is feasible and safe. One risk is that because the T cells we make are not a complete genetic ( HLA ) match for the recipient, they might attack the subject and cause a condition called graft versus host disease (GVHD). We will closely monitor for this complication. Secondary objectives are to determine the effects of the T cell infusion on the virus infection and to see if the recipients can stay immune to these viruses. We will also see how long the T cells survive. Most closely HLA-matched multivirus specific CTL lines obtained from a bank of allogeneic viral specific cell lines will have antiviral activity against EBV, CMV, and adenovirus. The primary purpose of the study is to assess the safety of administering CHM-CTLs in transplant patients with EBV, CMV, or adenovirus infection.

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表示。列出的机构是 对于中心，这不一定是调查员的机构。 当患者受到供体的血压干细胞移植（HSCT）的治疗，这是治疗血液癌或其他血液疾病的最佳匹配，他们有感染的风险，直到他们可以从供体中产生新的免疫系统为止。在此期间，他们可能会因爱泼斯坦Barr病毒（EBV），巨细胞病毒和腺病毒而形成严重的病毒感染，这是可能引起问题的三种最常见病毒。研究人员先前已经表明，可以从移植供体中长大特殊的T细胞，称为病毒特异性CTL，这些供体可以预防和治疗这些病毒感染后将其归还给患者。但是，要种植这些细胞需要2-3个月的时间，因此，对于每个患有其中一种病毒感染的患者，从移植供体中种植病毒特异性CTL并不是实际的选择。 在这项研究中，研究人员将看到一种替代方法是否是从普通供体中制造病毒特异性CTL的库，如果他们开发了这些病毒感染之一，则可以冷冻的受试者进行冻结，然后可以治疗移植后的受试者。 病毒特异性的CTL系将从普通供体中生长并冷冻。为了制作CTL线，我们首先用特殊产生的腺病毒（载体）感染称为单核细胞的血细胞，该腺病毒（载体）也带有一部分巨细胞病毒（CMV）基因。这是一种残疾病毒，一旦发生感染就无法自身再现，因此无法扩散。 然后，这些感染的单核细胞刺激T细胞对腺病毒和CMV反应，并杀死感染这些病毒的细胞。然后，我们使用还感染了EBV的细胞（通过在实验室中感染EBV来从供体血液中产生的细胞），对T细胞进行了第二次刺激，以便细胞现在识别三种病毒CMV，EBV和腺病毒。一旦我们制作了足够数量的T细胞，我们将测试它们，以确保它们杀死感染这些病毒的细胞并冷冻它们。 如果移植患者感染其中一种病毒，并且尽管有标准治疗，感染仍然存在，则他或她有资格获得适当匹配的CTL系列。 主要目的是确定此策略是否可行且安全。一种风险是，因为我们制造的T细胞不是接受者的完全遗传（HLA）匹配，所以他们可能会攻击受试者并引起称为移植与宿主疾病（GVHD）的疾病。我们将密切监视这种并发症。 次要目标是确定T细胞输注对病毒感染的影响，并查看受体是否可以保持对这些病毒的影响。我们还将看到T细胞存活多长时间。 从A获得的最紧密的HLA匹配多病毒特异性CTL线 同种异体病毒特异性细胞系的库将对EBV，CMV和腺病毒具有抗病毒活性。 该研究的主要目的是评估在EBV，CMV或腺病毒感染的移植患者中施用CHM-CTL的安全性。