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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们建议开发和测试一种用于EB病毒阳性霍奇金病(HD)和非霍奇金S淋巴瘤(NHL)的过继免疫治疗的创新方法。我们先前已经证明过继转移供者来源的EBV特异性细胞毒性T淋巴细胞是治疗和治疗骨髓移植后EBV相关淋巴增生性疾病的有效方法。在证明移植后淋巴组织增生(LPD)中的EBV阳性细胞对免疫治疗敏感后，我们假设霍奇金病中的恶性细胞和免疫功能正常的患者中出现的EBV相关性NHL也是合适的免疫治疗靶点。我们已经评估了EBV特异性CTL的使用，它识别这些患者中所有9个潜在的EBV抗原，并在一些患者中显示出持久性、抗EBV免疫增强和抗肿瘤反应的证据。在目前的方案中，我们将检验这样一个假设，即针对这些肿瘤细胞表达的LMP2a抗原具有明确特异性的CTL株(LMP2特异性CTL)是安全的，可以增强患者对EBV编码抗原的免疫应答，并具有抗肿瘤作用。 具体目的：1)检测复发的S或非霍奇金S淋巴瘤患者自体LMP2A特异性细胞毒T淋巴细胞(CTL)的安全性。这些CTL可能带有逆转录病毒载体导入的新霉素耐药基因。2)检测LMP2A特异性细胞毒T淋巴细胞系的存活率和免疫功能。3)评估LMP2A特异性CTL的抗病毒和抗肿瘤作用。4)获得延长剂量方案的安全性和应答性的初步信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. 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. 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.