Novel Strategies for Brain Tumor Therapy

脑肿瘤治疗新策略

• 批准号: 7577562
• 负责人: Ian F. Pollack
• 金额: $ 94.99万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7577562
• 关键词: Novel; Strategies; Brain; Tumor; Therapy

DESCRIPTION (provided by applicant): The prognosis for patients with malignant brain tumors has improved minimally in the last two decades; median survival is less than one year for patients with malignant glioma, the most common primary brain tumor. These statistics provide a strong rationale for coordinated efforts to identify innovative approaches to treat these tumors. The unifying hypothesis of this program project is that novel therapeutic strategies that take into account the unique features of these tumors will induce tumor regression, and potentiate conventional therapies. Each project is translationally oriented, with a common goal of addressing fundamental biological issues relevant to tumor growth and evaluating innovative treatment approaches using a series of preclinical models, as a basis to identify promising strategies to advance into clinical therapies. Project 1 is based on the hypothesis that inhibition of aberrantly activated signal transduction pathways, or activation of apoptosis signaling, will induce glioma cell killing, potentially in a genotype-specific fashion, and that this approach will have independent activity in glioma models, and potentiate other approaches. Project 2 postulates that vaccination with glioma-associated antigen epitopes, in conjunction with systemic therapy designed to enhance immunoreactivity in the brain tumor microenvironment, will be an effective mechanism for antigen delivery to antigen-presenting cells, and that the conditions for immunization can be optimized using signaling or vector-mediated strategies that promote dendritic cell maturation and function, in collaboration with Projects 1 and 3. Project 3 postulates that gene delivery to the brain tumor microenvironment, using oncolytic Herpes virus vectors incorporating novel multigene constructs engineered to facilitate virus incorporation, spread, and transduction efficiency, can achieve tumor killing and enhance the effects of other treatment strategies. This project will also generate many of the vector constructs that will be used in Projects 1 and 2. The Administrative/Biostatistics/Clinical Support Core (A) provides essential infrastructure support for the activities of this program. The Cellular and Tissue Imaging Core (B) provides a panoply of advanced microscopic imaging capabilities used in each of the projects. The Immunological Monitoring and Cellular Products Laboratory Core (C) provides banking of tissue and serum samples, maintenance of cell lines, preparation of biological products, and therapeutic monitoring essential for the clinical protocols in this program. Relevance: Taken together, the multidisciplinary interactions that have evolved in this program optimize our chances to identify and refine promising approaches that can be applied clinically to improve the prognosis of patients with malignant gliomas.

描述（由申请人提供）： 在过去的二十年中，对恶性脑肿瘤患者的预后有所改善。对于最常见的原发性脑肿瘤，患有恶性神经胶质瘤的患者的中位生存期少于一年。这些统计数据为确定治疗这些肿瘤的创新方法的协调努力提供了强有力的理由。该计划项目的统一假设是，考虑到这些肿瘤的独特特征的新型治疗策略将诱导肿瘤回归，并增强常规疗法。每个项目都是以翻译为导向的，一个共同的目标是解决与肿瘤生长有关的基本生物学问题，并使用一系列临床前模型评估创新的治疗方法，以此作为确定有望促进临床疗法的有希望的策略。项目1基于以下假设：抑制异常激活的信号转导途径或凋亡信号的激活将诱导胶质瘤细胞杀伤，可能以基因型特异性方式诱导，并且这种方法将在神经胶质瘤模型中具有独立的活性，并增强其他方法。项目2假定，与胶质瘤相关的抗原表位接种以及旨在增强脑肿瘤微环境中免疫反应性的全身治疗，将是抗原递送到抗原启用细胞的有效机制，以及使用抗原促成的细胞的条件，可以使用信号或促进的策略进行促进的策略，以使促进的策略达到促进的策略，使其具有促进的促进性，该策略是促进的，该策略是促进的，该策略是促进的，该策略是促进的，该策略是促进的，该策略是促进的，该策略是抗原的细胞，使得降级降级，项目1和3。项目3假定该基因递送到脑肿瘤微环境，使用溶瘤疱疹病毒载体，这些病毒载体结合了设计的新型多基因构建体，该构造设计为促进病毒掺入，扩散和转导效率，可以实现肿瘤杀伤并增强其他治疗策略的影响。该项目还将生成许多将在项目1和2中使用的向量结构。行政/生物统计学/临床支持核心（a）为该计划的活动提供了基本的基础架构支持。细胞和组织成像核心（B）提供了每个项目中使用的先进微观成像功能的套餐。免疫监测和细胞产品实验室核心（C）提供了组织和血清样品的文献，维持细胞系，生物产品的制备以及该程序中临床方案必不可少的治疗监测。相关性：综上所述，该计划中进化的多学科相互作用优化了我们的机会，以识别和完善有希望的方法，可以在临床上应用这些方法来改善恶性神经胶质瘤患者的预后。