PROCUREMENT OF TISSUE FOR MAKING EPSTEIN-BARR VIRUS (EBV) SPECIFIC CYTOTOXIC T

采购用于制备 Epstein-Barr 病毒 (EBV) 特异性细胞毒性 T 的组织

• 批准号: 8166709
• 负责人: HELEN E HESLOP
• 金额: $ 0.11万
• 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/8166709
• 关键词: Animals; Antibodies; Antigens; B-Lymphocytes; Back; Blood; Body Fluids; Bone Marrow Transplantation; CD8B1 gene; Cells; Chronic; Companions; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic T-Lymphocytes; Defense Mechanisms; Development; Donor person; EBV-Specific Cytotoxic T-Lymphocyte; EBV-associated disease; Epithelial Cells; Epstein-Barr Virus Infections; Fatigue; Fever; Funding; Future; Genome; Grant; Growth; Hepatosplenomegaly; Herpesviridae; Hodgkin Disease; Human; Human Herpesvirus 4; Immune; Immune response; Immune system; Immunologic Monitoring; In Vitro; Individual; Infection; Infectious Mononucleosis; Institution; LMP1; Life; Lymphoma; Lymphoproliferative Disorders; Malignant Neoplasms; Mediating; Membrane Proteins; Nasopharynx Carcinoma; Nuclear Antigens; Organ Transplantation; Oropharyngeal; Patients; Peptide Fragments; Population; Proteins; Protocols documentation; Research; Research Personnel; Resources; Risk; Saliva; Serum; Solid; Source; Surface; Syndrome; System; T-Lymphocyte; Tissue Procurements; Tissues; United States National Institutes of Health; Viral Antigens; Virus; acquired immunodeficiency; cancer cell; cytotoxic; immunosuppressed; infected B cell; lytic replication; prevent; research study; response; transmission process

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. This is a procurement only protocol This is a companion protocol to the following GCRC supported research studies: H-9935, 6676, 9454, 8216 Using blood obtained from eligible subjects, will enable the ability to produce EBV specific cytotoxic T lymphocytes (CTLs). The objective of this protocol is to obtain tissue (blood) for the purpose of making EBV specific cytotoxic T lymphocytes (CTLs). If successful, these cells may be given back to the patient in the future should they become eligible for one of the EBV-CTL research studies being conducted. Epstein-Barr virus (EBV) is a human lymphotropic herpes virus able to infect and immortalize human B lymphocytes. In the primary infection, occurring via saliva exchange, EBV infects oropharyngeal epithelial cells that support the lytic replication and allow the transmission of the virus to circulating B cells. Once in the B cells, the EBV genome is maintained in a latent form. B cells infected with EBV in vitro undergo transformation as result of the expression of latency-associated transforming proteins. These B cells always express a number of EBV gene products including the nuclear antigens EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA 3C, EBNA LP and the latent membrane proteins LMP1 and LMP2. The proliferation of EBV-infected cells expressing these latency-associated transforming proteins is controlled by specific T cells. Hence, in a majority of the population, primary infection is asymptomatic or results in a mild and self-limiting illness (infectious mononucleosis, IM). Following infection, individuals are life-long virus carriers. Unlike patients with a normal immune system, people with congenital or acquired immunodeficiency are highly susceptible to the development of EBV driven lymphoproliferative disease (EBV-LPD) since the reactivation of EBV is less tightly controlled by a cell-mediated response. Evidence suggests that EBV specific CD8+ CTLs are the most important defense mechanism against outgrowth of EBV infected B cells. These cells recognize peptide fragments derived from viral antigens expressed in association with MHC molecules on the surface of B cells. The state of reduced or suppressed T cell activity in immunosuppressed individuals interferes with the immunosurveillance system and increases the risk of EBV-driven proliferation of the infected cells, allowing Bcell clones with a growth advantage to emerge and result in one or more clonal populations. Another syndrome associated with defective immune control of EBV is severe chronic active EBV (SCAEBV) infection syndrome where patients present with chronic fatigue, fever, hepatosplenomegaly and lymphoadenopathy . Patients characteristically have elevated antibody titers to the viruscapsid antigen and low or absent antibody to EBNA and free virus in serum or other body fluids. EBV is also associated with other malignancies and is found in the malignant cells of 40% of patients with Hodgkin Disease, and most cases of nasopharyngeal carcinoma. Studies in animals and humans have shown that EBV specific T-cells can be generated ex-vivo to produce an anti- EBV infected cell immune response. We have used this approach in patients post bone marrow transplant where donor derived EBV-specific CTLs have been effective both in preventing and treating EBV lymphoproliferation. We are now extending this approach to other EBV-associated diseases including EBV lymphomas arising after solid organ transplant, EBV positive Hodgkin disease, nasopharyngeal carcinoma and severe chronic EBV 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代表。列出的机构是 对于中心，这不一定是调查员的机构。 这是仅采购协议 这是以下GCRC支持研究的同伴协议： H-9935，6676，9454，8216使用从合格受试者获得的血液，将使能够产生EBV特异性细胞毒性T淋巴细胞（CTLS）。 该方案的目的是获得组织（血液），以使EBV特异性细胞毒性T淋巴细胞（CTL）。如果成功的话，这些细胞将来可能会退还给患者，如果它们有资格参加正在进行的EBV-CTL研究之一。 爱泼斯坦 - 巴尔病毒（EBV）是一种能够感染和永生的人类B淋巴细胞的人淋巴疱疹病毒。在主要感染中，通过唾液交换发生，EBV感染了支持裂解复制并允许病毒传播B细胞的口咽上皮细胞。一旦进入B细胞，EBV基因组就会以潜在形式保持。 B细胞在体外感染了EBV 由于潜伏相关转化蛋白的表达而转化。这些B细胞始终表达许多EBV基因产物，包括核抗原EBNA1，EBNA2，EBNA3A，EBNA3B，EBNA3B，EBNA 3C，EBNA LP和潜在的膜蛋白LMP1和LMP2。表达这些潜伏相关转化蛋白的EBV感染细胞的增殖受到特定T细胞的控制。因此，在大多数人群中，原发性感染是无症状的，或导致轻度和自限性疾病（感染性单核细胞增多症，IM）。感染后，个体是终身病毒携带者。与患有正常免疫系统的患者不同，先天性或获得性免疫缺陷的人非常容易受到EBV驱动的淋巴增生性疾病（EBV-LPD）的发展，因为EBV的重新激活不受细胞介导的反应的紧密控制。证据表明，EBV特异性CD8+ CTL是针对EBV感染B细胞生长的最重要的防御机制。这些细胞识别与B细胞表面上与MHC分子相关的病毒抗原产生的肽片段。免疫抑制个体中T细胞活性降低或抑制的状态会干扰免疫监视系统，并增加受感染细胞EBV驱动的增殖的风险，从而使BCELL克隆具有生长优势并导致一个或多个克隆人群。与EBV免疫控制有缺陷有关的另一种综合征是严重的慢性活性EBV（SCAEBV）感染综合征，其中患者患有慢性疲劳，发烧，肝肾上腺肿瘤和淋巴结腺病。患者的特征性具有升高的对病毒抗原抗原的抗体滴度升高，在血清或其他体液中对EBNA的抗体或不存在抗体。 EBV也与其他恶性肿瘤有关，并且在40％的霍奇金疾病患者和大多数鼻咽癌病例的恶性细胞中发现。对动物和人类的研究表明，EBV特定的T细胞可以在体外产生以产生抗EBV感染的细胞免疫反应。我们已经在骨髓移植后使用了这种方法，其中源自EBV特异性CTL的供体在预防和治疗EBV淋巴细胞增生方面都是有效的。现在，我们将这种方法扩展到其他与EBV相关的疾病，包括固体器官移植后产生的EBV淋巴瘤，EBV阳性Hodgkin疾病，鼻咽癌和严重的慢性EBV感染。