T-CELL IMMUNOTHERAPY OF EBV ASSOCIATED LYMPHOMA

EBV 相关淋巴瘤的 T 细胞免疫治疗

• 批准号: 2106106
• 负责人: Martin J Cannon
• 金额: $ 11.49万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2106106
• 关键词: Epstein Barr virus; acquired immunodeficiency; cellular immunity; cytokine; cytotoxic T lymphocyte; gene expression; genetically modified animals; human subject; immunotherapy; laboratory mouse; lymphoma; passive immunization; tissue /cell culture; tissue mosaicism; virus related neoplasm /cancer

Epstein-Barr virus (EBV) is closely associated with the lymphomas and lymphoproliferative disorders (LPD) that arise in patients with acquired immunodeficiency. EBV is associated with the majority of AIDS-related immunoblastic lymphomas and virtually all cases of post-transplant lymphoma and LPD. Latent EBV infection in normal individuals is controlled by EBV-specific CD8+ T cell surveillance, and EBV-associated lymphoma and LPD in the immunodeficient is thus thought to arise as a result of impaired EBV-specific T cell immunity. In the light of these observations, this proposal will explore the potential for EBV-specific CD8+ T cell immunotherapy, using the SCID/hu mouse model of EBV-associated human B cell LPD. The SCID/hu mouse closely resembles the EBV-associated large-cell immunoblastic lymphoma that arise in the immunodeficient. There is in essence a single goal of this proposal; generation of well- characterized EBV-specific T cell lines or clones that can inhibit or reverse EBV-driven tumor development in SCID/hu mice. Two approaches will be considered: 1. Transfer of EBV-specific human CD8+ T cells to SCID mice bearing autologous EBV-induced human B cell tumors arising from injection of EBV- transformed lymphoblastoid cell lines (LCL). 2. Transfer of EBV-specific mouse CD8+ T cells. HLA A2.1/Kb transgenic mice will be primed to give and EBV-specific T cell response that recognizes HLA A2.1-expressing LCL. This strategy has the major advantage of allowing same-species T cell transfer experiments, facilitating reconstitution and evaluation of long-term EBV-specific T cell immunity in the context of severe immunodeficiency. T cell specificity and function will be characterized, and mechanisms of tumor inhibition will be investigated. T cells will be transferred at various times to assess therapy of early or advanced stages of disease; prevention reconstitution of EBV-specific T cell immunity will also be investigated. Strategies for enhancement of T cell engraftment and function in vivo will be explored. The principles established in this study will provide valuable information for the rational design of T cell immunotherapy for prevention or treatment of EBV-associated LPD and lymphoma in the setting of acquired immunodeficiency, most particularly transplant recipients and AIDS patients.

eb病毒（EBV）与淋巴瘤和恶性肿瘤密切相关