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.

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