IFN Gamma Induced Angiostatic Chemokines

γ干扰素诱导的血管抑制趋化因子

• 批准号: 6621413
• 负责人: Ravindra Uppaluri
• 金额: $ 12.17万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-14 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621413
• 关键词: IP 10 protein; angiogenesis inhibitors; fibrosarcoma; gene induction /repression; gene targeting; genetically modified animals; immunogenetics; interferon gamma; laboratory mouse; monoclonal antibody; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neutralizing antibody; nonhuman therapy evaluation

DESCRIPTION (provided by applicant): The candidate, Dr. Ravindra Uppaluri, is a faculty member in Otolaryngology at Washington University. Dr. Uppaluri's u l timate goal is to become an independent investigator studying the interaction of the immune system and head and neck malignancies. To achieve this goal he joined the laboratory of Dr. Robert Schreiber to pursue training in tumor immunology. The training plan includes a dedicated mentor, an intensive laboratory experience, and additional course work and seminars to complement the candidate's development. Dr. Schreiber's laboratory has demonstrated the existence of an interferon gamma (IFN-gamma) and lymphocyte- dependent tumor surveillance system that is operative in preventing many types of mouse tumors. This model requires the action of endogenously produced IFN- gamma. Two actions of IFN-gamma have been proposed: first, its capacity to regulate immunogenicity of tumors; and second, its capacity to force the tumor to produce angiostatic chemokines such as IP-10, Mig, and I-TAC. The purpose of this proposal is to critically test whether IFN-gamma-induced angiostasis plays an obligate role in mediating tumor surveillance and to establish the temporal relationship between IFN-gamma's abilities to effect angiostasis versus immunogenicity. To achieve this goal, the project will pursue three specific aims. In Specific Aim 1, the effects of IP-10, Mig and I-TAC on IFN- g a m m a-sensitive and insensitive tumor growth will be assessed both individually and collectively by transplanting tumors in mice that have been treated with monoclonal antibodies to block IP-10, Mig and I-TAC. Specific Aim 2 will address the effects of enforced and inducible expression of IP-10 on tumor growth. Specific Aim 3 will address the requirement of lymphocytes for tumor growth and regression in the context of IP-10 and define the relative contribution of angiostasis in immunization of the mouse to tumor. This work should provide a clear picture of events that lead to host defense against cancer.

描述（由申请人提供）：候选人Ravindra Uppaluri博士是 华盛顿大学耳鼻喉科学院成员。 Uppaluri博士 目标是成为研究的独立调查员 免疫系统以及头部和颈部恶性肿瘤的相互作用。 实现 这个目标他加入了罗伯特·施雷伯（Robert Schreiber）博士的实验室进行培训 在肿瘤免疫学中。 培训计划包括专门的导师 密集的实验室经验以及其他课程工作和研讨会 补充候选人的发展。 Schreiber博士的实验室 证明了干扰素伽马（IFN-GAMMA）和淋巴细胞的存在 依赖性肿瘤监视系统可防止多种类型 小鼠肿瘤。 该模型需要内源产生的IFN-的作用 伽玛。 提出了IFN-Gamma的两种动作：首先，其能力 调节肿瘤的免疫原性；其次，它迫使肿瘤的能力 产生血管静态趋化因子，例如IP-10，MIG和I-TAC。 目的 该提议的重要性是批判性测试IFN-GAMMA诱导的AngioStasis是否 在介导肿瘤监测并确定肿瘤监测方面起着强大的作用 IFN-Gamma实现Angiostis的能力之间的时间关系 与免疫原性相对于免疫原性。 为了实现这一目标，该项目将追求三个 具体目标。 在特定目标1中，IP-10，MIG和I-TAC对IFN-的影响 g a m a敏感和不敏感的肿瘤生长将被评估 通过在小鼠中移植肿瘤的单独和集体 用单克隆抗体处理以阻断IP-10，MIG和I-TAC。 具体的 AIM 2将解决IP-10的强制和诱导表达的影响 关于肿瘤生长。 特定目标3将满足淋巴细胞的需求 对于IP-10的背景下的肿瘤生长和回归，并定义 血管痛在小鼠对肿瘤免疫中的相对贡献。 这项工作应清楚地了解导致主机防御的事件 反对癌症。