Non-Invasive Markers of Tumor Response: A Study of Anti-Angiogenic Therapy

肿瘤反应的非侵入性标志物：抗血管生成治疗的研究

基本信息

批准号：
7729463
负责人：
JASON Arthur KOUTCHER
金额：
$ 12.47万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7729463
关键词：
Address Aftercare Angiogenesis Inhibitors Antigens Area Biological Markers Biology Blood Vessels Cell Communication Cell Therapy Chemosensitization Choline Choline Kinase Class Clinic Clinical Clinical Research Contrast Media Cyclotrons Data Analyses Development Dose Drug Delivery Systems Endothelial Cells Epstein-Barr Virus-Related Lymphoma Evaluation Fluorouracil Funding Gene Expression Genetic Goals Growth Heat-Shock Proteins 90 Human Image Imaging Techniques Institution Intercellular Fluid Invasive Kinetics Laboratories Lead Magnetic Resonance Malignant neoplasm of prostate Measurement Measures Memorial Sloan-Kettering Cancer Center Metabolism Metastatic Prostate Cancer Methodology Methods Modeling Molecular Biology Monitor Mus New Agents Outcome Oxygen measurement, partial pressure, arterial PECAM1 gene Patients Pericytes Permeability Pharmaceutical Preparations Pharmacodynamics Physiology Positron-Emission Tomography Prostate Quality Indicator Radiation Radiochemistry Rate Reporter Genes Research Infrastructure Resistance Resources Respiration Signal Transduction Inhibitor Site Smooth Muscle Solid Neoplasm T-Lymphocyte Time Translations Tumor Burden Tumor Markers Vascular Permeabilities Viral Viral Vector Work Xenograft procedure base career chemotherapy cytokine improved in vivo in vivo Cellular and Molecular Imaging Centers inhibitor/antagonist man molecular imaging neoplastic novel oncology pressure radioligand receptor response subcutaneous success treatment duration tumor tumor growth uptake

项目摘要

This response to PAR-04-069, is a renewal application based on work begun during the original period of ICMIC funding at MSKCC The central theme of this new proposal is translation of the progress we have made into clinical research and application in oncology. Two focus areas are proposed which build on the success of the past funding period: a) human reporter gene constructs will be developed and used to study and better understand T cell interactions and activation in adoptive T cell therapy in patients, (Projects 1 and 2), and b) molecular imaging of the key molecules relevant to assessing drug treatment response, particularly for signal transduction inhibitors, and especially in solid tumors (Projects 3-5). Reporter gene imaging applications in adoptive cell therapy, including targeting of CD4 and CDS sub-types and chimeric Tcells with T-cells with artificial reactivity to prostate cancer, will be studied in man using human derived reporter genes (P1 and P2): Imaging T cell interactions in adoptive therapy of EBV-associated lymphoma (R. Blasberg, Project 1 leader; R. O'Rielly, co-leader), and PET imaging of survival, activation, and response to cytokine stimulation of genetically retargeted prostate specific T cells (V. Ponomarev, Project 2 leader; M. Sadelain, co-leader). In Project 3, high field MRI/MRS will probe the pharmacodynamics of in vivo drug conversion and metabolism, to predict sensitivity for an important new class of angiogenesis inhibitors, and to develop of non-invasive markers (J. Koutcher, Project 3 leader). In Projects 4 and 5, Positron Emission Tomography (PET) based molecular imaging methods will study the biology of treatment response, using novel radioligands for aridrogen receptor, her2, and heat shock protein 90. The development of methodologies for the in vivo imaging of the effects of novel inhibitors of signal transduction for translation to the clinic (N. Rosen, Project 3 leader; D. Solit, co-leader), and molecular imaging of castrate-resistant metastatic prostate cancer (S. Larson, Project 5 leader; H. Scher and P. Smith-Jones, coleaders). Translational developmental projects, oncology based career development, and molecular biology, radiochemistry/cyclotron and data analysis research resources provide essential infrastructure. In summary, novel molecular imaging paradigms will be used to address important clinical questions in oncology.

此对 PAR-04-069 的回复是基于原始期间开始的工作的续展申请。 MSKCC 的 ICMIC 资助这项新提案的中心主题是转化我们所取得的进展已进入肿瘤学的临床研究和应用。在此基础上提出了两个重点领域过去资助期的成功：a) 将开发人类报告基因构建体并用于研究并更好地了解患者过继性 T 细胞治疗中的 T 细胞相互作用和激活（项目 1 2) 和 b) 与评估药物治疗反应相关的关键分子的分子成像，特别是对于信号转导抑制剂，尤其是实体瘤（项目 3-5）。报告基因过继细胞疗法中的成像应用，包括靶向 CD4 和 CDS 亚型以及嵌合 T 细胞具有对前列腺癌具有人工反应性的 T 细胞，将使用人源性在人体中进行研究报告基因（P1 和 P2）：EBV 相关淋巴瘤过继治疗中 T 细胞相互作用的成像（R. Blasberg，项目 1 负责人；R. O'Rielly，联合负责人），以及生存、激活和恢复的 PET 成像基因重定向前列腺特异性 T 细胞对细胞因子刺激的反应（V. Ponomarev，项目 2 领导者; M.萨德兰，联合领导）。在项目3中，高场MRI/MRS将探测体内药效学药物转化和代谢，以预测一类重要的新型血管生成抑制剂的敏感性，并开发非侵入性标记（J. Koutcher，项目 3 负责人）。在项目 4 和 5 中，正电子基于发射断层扫描 (PET) 的分子成像方法将研究治疗的生物学反应，使用针对干旱激素受体、her2 和热休克蛋白 90 的新型放射性配体。开发新型信号转导抑制剂的体内成像方法用于翻译到临床（N. Rosen，项目 3 负责人；D. Solit，联合负责人），以及分子成像去势抵抗性转移性前列腺癌（S. Larson，项目 5 负责人；H. Scher 和 P. Smith-Jones，共同负责人）。转化发展项目、基于肿瘤学的职业发展和分子生物学，放射化学/回旋加速器和数据分析研究资源提供了必要的基础设施。在总之，新颖的分子成像范式将用于解决重要的临床问题肿瘤学。