Biological Imaging Core

生物成像核心

• 批准号: 7782254
• 负责人: JOHANNES CZERNIN
• 金额: $ 35.53万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 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 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7782254
• 关键词: Acyclovir; Adoptive Cell Transfers; Adoptive Transfer; Affinity; Animal Cancer Model; Animal Model; Arts; Biological; Bioluminescence; Cell Count; Cell Cycle Kinetics; Cell Therapy; Cells; Clinical; Clinical Immunology; Clinical Protocols; Clinical Trials; Collaborations; Complement; Consensus; Data; Data Analyses; Deposition; Development; Diagnostic; Engineering; Generations; Genetic; Goals; Guanine; Hematopoietic stem cells; Herpesvirus 1; Human; Image; Imaging Techniques; Immune response; Immunologic Monitoring; Immunotherapy; In Vitro; Institution; Kinetics; Life; Lymphocyte; Lymphoid; Malignant Neoplasms; Mature T-Lymphocyte; Measurement; Metastatic Melanoma; Methods; Modeling; Modification; Monitor; Optics; Organ; Organism; Patients; Population; Positron-Emission Tomography; Program Research Project Grants; Protocols documentation; Reporter Genes; Reporting; Reproducibility; Research; Research Infrastructure; Research Personnel; Resolution; Sampling Errors; Scanning; Signal Transduction; Site; Stem cell transplant; Structure; System; T-Lymphocyte; Techniques; Technology; Therapeutic; Thymidine Kinase; Transplantation; Treatment Efficacy; Variant; Work; X-Ray Computed Tomography; abstracting; analog; base; cancer cell; cancer immunotherapy; cellular engineering; data acquisition; gene therapy; genetically modified cells; imaging modality; improved; in vivo; melanoma; molecular imaging; novel; optical imaging; peripheral blood; pre-clinical; programs; research study; response; scientific organization; software systems; suicide gene; tool; trafficking; tumor; whole body imaging

ABSTRACT: Novel adoptive T cell therapies have enabled long lasting objective clinical responses in a significant proportion of patients with metastatic melanoma. Treatment efficacy and availability could be further improved by ex vivo genetic modification of lymphocytes allowing generation of large numbers of cells with enhanced anti-tumor function. The development of such adoptive cell transfer immune therapies is critically dependent on the availability of tools to track the distribution of genetically modified lymphocytes following transplantation in melanoma patients. Work by Program Project Grant (PPG) Investigators in animal models of cancer and in humans has demonstrated that this goal could be accomplished using novel molecular imaging techniques such as Positron Emission Tomography (PET). To visualize the distribution of genetically modified T lymphocytes and Hematopoietic Stem Cells transplanted in melanoma patients, these cells will be engineered to express a PET reporter gene derived from the Herpes Simplex Virus 1 thymidine kinase (HSVI-tk). HSVI-tk has been used extensively in clinical trials as a "suicide gene" and has a very high affinity for the PET probe (9-[4-[(18)F]fluoro-3-(hydroxymethyl)-butyl]guanine) (9(18)'F]FHBG). [9(18)F]FHBG administered in trace amounts accumulates specifically in cells expressing HSVI-tk and resulting signals can be detected by PET. We will use this technique for in vivo "counting" of genetically modified cells at various sites throughout the body, including lymphoid organs and metastatic melanoma deposits. Such measurements cannot be performed using conventional technologies and could provide eariy prediction markers for therapeutic responses. To support imaging studies by PPG Investigators, we propose to establish a Biological Imaging Core for noninvasive monitoring of immune responses. This Core will complement state-of-the-art 'in vitro' immUne monitoring measurements described in Core A and will enable PPG Investigators to pertorm preclinical and clinical 'in vivo' immune monitoring studies using multiple imaging modalities. The proposed Core will take advantage of the unique expertise and infrastructure for functional and anatomical tomographic imaging already available at UCLA and will also coordinate preclinical imaging experiments performed at other participating institutions. We envision that the Imaging Core will help cement long-term interactive multi-institutional collaborations involving experts in imaging, gene therapy, basic and clinical immunology, who are at the forefront of cancer immunotherapy transitional research.

摘要：新型的TEPNIDE T细胞疗法已使大部分转移性黑色素瘤患者的长期持久客观临床反应。通过体内遗传修饰的淋巴细胞可以进一步提高治疗功效和可用性，从而使抗肿瘤功能增强的大量细胞产生大量细胞。这种收养细胞转移免疫疗法的发展取决于在黑色素瘤患者移植后追踪转基因淋巴细胞分布的工具的可用性。计划项目赠款（PPG）研究人员在癌症和人类动物模型中的研究表明，可以使用新颖的分子成像技术（例如正电子发射断层扫描（PET））来实现这一目标。 为了可视化在黑色素瘤患者中移植的转基因T淋巴细胞和造血干细胞的分布，这些细胞将被设计为表达源自源自单纯疱疹病毒1胸苷激酶（HSVI-TK）的宠物报告基因。 HSVI-TK已在临床试验中广泛用于“自杀基因”，并且对PET探针（9- [4- [（（18）F] Fluoro-3-（羟基甲基） - 丁基） - 丁氨酸）具有很高的亲和力（9（18）'F] FHBG）。 [9（18）f]以痕量为单位的FHBG在表达HSVI-TK的细胞中累积了，可以通过PET检测到所得信号。我们将使用此技术进行体内“计数”遗传学上的“计数” 整个体内各个部位的修饰细胞，包括淋巴器官和转移性黑色素瘤 沉积物。这样的测量不能使用常规技术进行，并且可以提供耳语 治疗反应的预测标记。 为了支持PPG研究者的成像研究，我们建议建立无创的生物成像核心 监测免疫反应。该核心将补充最先进的“体外”免疫 核心A中描述的监视测量值，并将使PPG研究者能够临时临床前和 临床“体内”免疫监测研究，使用多种成像方式。 提出的核心将利用功能和解剖学的独特专业知识和基础架构 UCLA已经可用的层析成像成像，还将协调临床前成像实验 在其他参与机构进行。我们设想成像核将有助于长期巩固 互动式多机构合作，涉及成像，基因疗法，基本和临床的专家 免疫学，在癌症免疫疗法过渡研究的最前沿。