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

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， 包括其它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。 假设 我们建议开发和测试一种创新的方法来过继免疫治疗EBV +ve霍奇金病（HD）和非霍奇金淋巴瘤（NHL）。我们以前已经证明，过继转移供体来源的EBV特异性细胞毒性T淋巴细胞是骨髓移植后EBV相关淋巴组织增生性疾病的有效治疗和疗法。已经表明，在移植后淋巴细胞增殖（LPD）的EBV阳性细胞对免疫治疗敏感，我们假设，霍奇金病和EBV相关的NHL中产生的免疫功能正常的患者，表达更有限的库EBV编码的抗原，恶性细胞也是合适的免疫治疗的目标。我们已经评估了EBV特异性CTL的使用，其识别此类患者中的所有9种潜伏性EBV抗原，并显示出抗EBV免疫的持久性、增强和抗肿瘤应答的证据。在该当前方案中，我们将测试以下假设：具有针对由这些肿瘤细胞表达的LMP 2a抗原的确定特异性的CTL系（LMP 2特异性CTL）是安全的，增加患者对EBV编码抗原的免疫应答，并且具有抗肿瘤作用。 具体目标：1）确定自体LMP 2A特异性细胞毒性T淋巴细胞（CTL）在复发性霍奇金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抗性基因标记。2)确定LMP 2A特异性细胞毒性T淋巴细胞系的存活和免疫功能。3)评估LMP 2A特异性CTL的抗病毒和抗肿瘤作用。4)获得关于安全性和对扩展剂量方案的反应的初步信息。

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.