CLINICAL TRIAL: EBV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES FOR EBV-POSITIVE NASOPHARYN

临床试验：针对 EBV 阳性鼻咽的 EBV 特异性细胞毒性 T 淋巴细胞

• 批准号: 8166756
• 负责人: HELEN E HESLOP
• 金额: $ 0.08万
• 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/8166756
• 关键词: Adult; Aftercare; Age; Alkylating Antineoplastic Agents; Autologous Epstein-Barr Virus-Specific Cytotoxic T Lymphocytes; Cell Line; Cells; Child; Clinical Trials; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic T-Lymphocytes; Disease; Disease remission; Disease-Free Survival; EBV-Specific Cytotoxic T-Lymphocyte; Funding; Grant; Head and Neck Cancer; Human Herpesvirus 4; Hypothyroidism; Incidence; Institution; Malignant - descriptor; Minority; Nasopharynx Carcinoma; Nuclear Pore Complex; Patients; Proteins; Pulmonary Fibrosis; Race; Radiation; Radiation therapy; Refractory; Relapse; Research; Research Personnel; Resources; Risk; Safety; Second Primary Cancers; Source; Staging; Survival Rate; Taiwan; Time; Treatment Protocols; United States National Institutes of Health; advanced disease; alpha-Thalassemia; chemotherapy; cohort; follow-up; growth hormone deficiency; improved; intravenous injection; killings; lymphoblastoid cell line; malignant stomach neoplasm; medical complication; neoplastic; neoplastic cell; novel; outcome forecast; tumor

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. In this study we wish to generate polyclonal EBV specific cytotoxic T cells and adoptively transfer them to patients with active Nasopharyngeal Carcinoma. The lymphoblastoid cell lines, which are used to generate polyclonal CTLs, express the entire range of EBV derived gene products including LMP-1 and LMP-2. Although LMP-specific CTLs are in a minority, it is possible that even in small numbers they will have the ability to recognize and kill LMP-1 expressing cells including the NPC tumor cells. The Specific Aims of this project are: 1) To determine the feasibility of generating EBV specific cytotoxic T cell lines from patients with active Nasopharyngeal Carcinoma. 2) To determine the safety of two intravenous injections of autologous EBV specific cytotoxic T-lymphocytes (CTL) in patients with Nasopharyngeal Carcinoma. 3) To determine the survival, immunological efficacy and anti-tumor effects of EBV specific cytotoxic T-lymphocyte lines. Nasopharyngeal carcinoma, is a malignant disease with a variable range of incidence depending on age, geographical place, race and Epstein-Barr virus (EBV) exposure. It has an annual incidence of nearly 1 case per 100,000 children < 21yrs in the USA. For the majority (75-91%) of patients, the long-term prognosis is favorable with combined modality therapy. Of the 10-15% of patients who relapse after initial therapy, only 40% will enter a second remission. For the remainder who fail salvage chemotherapy or relapse for a second time, the prognosis is poor. In adults, the overall 5-year survival rates following radiotherapy are stage dependant and range from 70% to 80% for stage I, and 20-40% for stage IV. For more advanced disease, the use of combined modality therapy in adults results in an overall survival of 50%. Although overall survival rates are good in children, current treatment regimens are still far from ideal. Late medical complications after treatment for NPC include growth hormone deficiency, hypothyroidism and pulmonary fibrosis. A large restrospective study in Taiwan of a cohort of 1,549 patients was performed to assess the risk of secondary malignancies in NPC patients post radiotherapy +/- chemotherapy. The patients ranged in age from 10-80years (median 46.3years) with a maximum follow-up of 16 years. Fatal neoplastic complications included secondary leukemia related to alkylating agent chemotherapy and head and neck cancers (most likely radiation induced), and gastric cancer. It is therefore desirable to develop novel therapies that could improve disease free survival in relapsed/refractory patients and which might ultimately reduce the incidence of long term treatment related complications in all patients.

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。 在这项研究中，我们希望产生多克隆EBV特异性的细胞毒性T细胞，并将其传递给活跃的鼻咽癌患者。用于生成多克隆CTL的淋巴细胞细胞系表达了包括LMP-1和LMP-2在内的EBV衍生基因产物的整个范围。 尽管LMP特异性的CTL属于少数群体，但即使在少数情况下，他们也有能力识别和杀死包括NPC肿瘤细胞在内的LMP-1表达细胞。 该项目的具体目的是：1）确定来自活性鼻咽癌患者的EBV特异性细胞毒性T细胞系的可行性。 2）确定两种自体EBV特异性细胞毒性T淋巴细胞（CTL）对鼻咽癌患者的两次静脉注射的安全性。 3）确定EBV特异性细胞毒性T淋巴细胞系的生存，免疫学和抗肿瘤作用。 鼻咽癌是一种恶性疾病，其发病率范围可变，具体取决于年龄，地理位置，种族和爱泼斯坦 - 巴尔病毒（EBV）暴露。在美国，它的年发病率近100,000名儿童<21岁。 对于大多数（75-91％）的患者，长期预后具有联合态疗法。在初始治疗后复发的10-15％的患者中，只有40％将进入第二次缓解。对于第二次打捞化疗或复发失败的其余部分，预后很差。在成年人中，放疗后的总5年生存率取决于阶段，I期为I期为70％至80％，IV期为20-40％。对于更晚期疾病，在成年人中使用合并的方式疗法的总生存率为50％。 尽管总体生存率在儿童中良好，但目前的治疗方案仍然远非理想。 NPC治疗后的晚期医疗并发症包括生长激素缺乏症，甲状腺功能减退症和肺纤维化。在台湾进行了一项大量约束性研究，该研究对1,549例患者进行了一组，以评估放疗后NPC患者的继发性恶性肿瘤的风险+/-化学疗法。患者的年龄从10-80岁（中值46.3岁）年龄不等，最大随访为16岁。致命的肿瘤并发症包括与烷基化剂化疗有关的继发性白血病和头颈癌（最有可能诱发的辐射）和胃癌。因此，希望开发出可以改善复发/难治性患者无疾病生存的新型疗法，这最终可能会减少所有患者长期治疗并发症的发生率。