EBV-SPECIFIC CTL AND LYMPHOMA IN SCID MICE

SCID 小鼠中的 EBV 特异性 CTL 和淋巴瘤

• 批准号: 2100052
• 负责人: RACHEL J BUCHSBAUM
• 金额: $ 7.61万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2100052
• 关键词: B lymphocyte; Epstein Barr virus; HIV infections; Herpesviridae disease; SCID mouse; cross immunity; cytotoxic T lymphocyte; disease /disorder model; flow cytometry; gene induction /repression; human subject; leukocyte adhesion molecules; lymphoma; microorganism immunology; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; nonhuman therapy evaluation; passive immunization; plaque assay; recombinant proteins; vaccinia virus; virus genetics; virus protein

This grant proposal is intended as a vehicle for preparing a hematologist/oncologist for a career in immunology research. The Physician Scientist Award will provide the financial support required to sustain this training period. The application is structured to provide the didactic and laboratory experiences necessary to succeed as an independent investigator. Coursework equivalent to that required for Ph.D. candidates will be pursued at the Tufts University Sackler School of Graduate Biomedical Sciences. Research will be performed under the supervision of Dr. Judy Lieberman, a hematologist well-versed in T cell immunology, and Dr. Robert Schwartz, an experienced immunologist. The sponsoring Division of Hematology/Oncology currently includes approximately 35 postdoctoral research fellows, and has an outstanding record for training medical investigators. The proposed research project will study the immune control of B cell neoplasia related to the Epstein-Barr virus. We will address the hypothesis that CD8+ T cells (CTL) provide protection against EBV- associated B cell lymphomas via recognition of latent cycle EBV proteins. This work will take advantage of viral-vaccinia technology allowing selection of cytotoxic T cells with precise specificities, as well as a small animal model of human EBV-associated B cell lymphoma. The project is organized in 4 parts: (1) describes the generation and characterization of CTL that recognize specific EBV latent proteins; (2) evaluates the use of EBV-specific CTL in adoptive therapy of EBV-associated tumors in a SCID mouse model; (3) asks whether adoptive therapy by CTL can lead to an escape from immune surveillance by a change in tumor cell expression of EBV-related proteins; (4) describes a population study in which a correlation will be sought between the spectrum of EBV-latent-protein- specific CTL and the development of EBV-positive lymphoma in humans.

该赠款提案旨在作为准备 免疫学研究职业的血液学家/肿瘤学家。医师 科学家奖将提供维持所需的财政支持 这个训练期。该应用程序的结构是提供 作为独立的成功所必需的教学和实验室经验 研究者。课程工作量等于博士所需的课程。候选人 将在塔夫茨大学萨克勒研究生中追踪 生物医学科学。 研究将在 朱迪·利伯曼（Judy Lieberman）博士，一位精通T细胞免疫学的血液学家， 经验丰富的免疫学家罗伯特·施瓦茨（Robert Schwartz）博士。赞助部门 目前的血液学/肿瘤学包括大约35个博士后 研究研究员，并在培训医疗方面有出色的记录 调查人员。 拟议的研究项目将研究B细胞的免疫控制 与爱泼斯坦 - 巴尔病毒有关的肿瘤。我们将解决 假设CD8+ T细胞（CTL）提供了针对EBV-的保护 相关的B细胞淋巴瘤通过识别潜在循环EBV蛋白。 这项工作将利用病毒 - 维卡西尼亚技术允许 选择具有精确特异性的细胞毒性T细胞以及A 人EBV相关B细胞淋巴瘤的小动物模型。 项目 在4个部分中组织：（1）描述了一代和表征 识别特定EBV潜在蛋白的CTL； （2）评估用途 EBV特异性CTL在SCID中与EBV相关肿瘤的过继疗法 鼠标模型； （3）询问CTL的收养疗法是否可以导致 通过改变肿瘤细胞表达的变化免疫监测 与EBV相关的蛋白质； （4）描述了一项人口研究，其中 将寻求EBV-Latent-蛋白质的光谱之间的相关性 特定的CTL和人类EBV阳性淋巴瘤的发展。