CLINICAL TRIAL: NEOMYCIN RESISTANCE LMP2A SPECIFIC CYTOTOXIC T-LYMPHOCYTES FOR

临床试验：新霉素耐药性 LMP2A 特异性细胞毒性 T 淋巴细胞

• 批准号: 8356765
• 负责人: Catherine M. Bollard
• 金额: $ 4.2万
• 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/8356765
• 关键词: Adoptive Immunotherapy; Adoptive Transfer; Antigens; Antitumor Response; Autologous; Autologous Epstein-Barr Virus-Specific Cytotoxic T Lymphocytes; Bone Marrow Transplantation; Cells; Clinical Research; Clinical Trials; Cytotoxic T-Lymphocytes; EBV-Specific Cytotoxic T-Lymphocyte; Funding; Grant; Hodgkin Disease; Immune response; Immunity; Immunocompetent; Immunotherapy; Lymphoproliferative Disorders; National Center for Research Resources; Neomycin; Neomycin resistance gene; Non-Hodgkin' s Lymphoma; Patients; Principal Investigator; Protocols documentation; Regimen; Relapse; Research; Research Infrastructure; Resistance; Resources; Retroviral Vector; Safety; Source; Specificity; Testing; Transplantation; United States National Institutes of Health; Viral; cancer cell; cost; dosage; effective therapy; immune function; innovation; neoplastic cell; response; 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. HYPOTHESIS We propose to develop and test an innovative approach to adoptive immunotherapy for EBV +ve Hodgkin disease (HD) and Non-Hodgkin's Lymphoma (NHL). We have previously shown adoptive transfer of donor derived EBV specific cytotoxic T lymphocytes is effective treatment and therapy for EBV associated lymphoproliferative diseases after bone marrow transplantation. Having shown that the EBV-positive cells in post-transplant lymphoproliferation (LPD) are susceptible to immunotherapy, we hypothesize that the malignant cells in Hodgkin disease and EBV associated NHL arising in immunocompetent patients, which express a more restricted repertoire of EBV encoded antigens, are also suitable targets for immunotherapy. We have already evaluated the use of EBV specific CTL, which recognize all 9 latent EBV antigens in such patients, and shown evidence of persistence, augmentation of anti-EBV immunity and evidence of antitumor response in some patients. In this current protocol, we will test the hypothesis that CTL lines with defined specificity against the LMP2a antigen expressed by these tumor cells (LMP2 specific CTLs) are safe, increase patient immune responses to EBV encoded antigens and have anti-tumor effects. SPECIFIC AIMS: 1) To determine the safety of autologous LMP2A-specific cytotoxic T-lymphocytes (CTL) in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. These CTLs may be marked with the neomycin resistance gene introduced by a retroviral vector. 2) To determine the survival and the immune function of LMP2A-specific cytotoxic T-lymphocyte lines. 3) To assess the anti-viral and anti-tumor effects of LMP2A-specific CTLs. 4) To obtain preliminary information on the safety and response to an extended dosage regimen.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 假设 我们建议开发和测试一种创新的EBV +VE Hodgkin病（HD）和非霍奇金淋巴瘤（NHL）的收养免疫疗法。我们先前已经表明，供体衍生的EBV特异性细胞毒性T淋巴细胞的产物转移是骨髓移植后的EBV相关淋巴增生性疾病的有效治疗和治疗。在证明移植后淋巴细胞增殖（LPD）中的EBV阳性细胞易受免疫疗法的敏感，我们假设在霍奇金病和EBV相关的NHL中，在免疫能力的患者中产生的恶性细胞与EBV相关患者的NHL相关的NHL，表达了EBV依次较大的EBV抗原抗原抗原术的抗原抗原范围，则适用于抗原抗原的目标。我们已经评估了EBV特异性CTL的使用，这些CTL在此类患者中识别所有9种潜在的EBV抗原，并显示出持久性的证据，抗EBV免疫的增强和某些患者的抗肿瘤反应的证据。在此目前的方案中，我们将测试以下假设：这些肿瘤细胞表达的LMP2A抗原（LMP2特异性CTL）是安全的，具有定义特异性的CTL线是安全的，增加了对EBV编码抗原的患者免疫反应并具有抗肿瘤作用。 具体目的：1）确定自体LMP2A特异性细胞毒性T-淋巴细胞（CTL）的安全性在复发性霍奇金（Hodgkin）或非霍奇金淋巴瘤患者中的安全性。这些CTL可以用逆转录病毒载体引入的新霉素耐药基因标记。 2）确定LMP2A特异性细胞毒性T淋巴细胞系的生存和免疫功能。 3）评估LMP2A特异性CTL的抗病毒和抗肿瘤作用。 4）获取有关对扩展剂量方案的安全性和反应的初步信息。