PET Imaging of Genetically Modified Human T-Cells in Prostate Cancer

此回复PAR-04-069，是一个基于在原始期间开始的工作的更新申请， 这一新提案的中心主题是将我们取得的进展转化为 用于肿瘤学的临床研究和应用。提出了两个重点领域， 过去的资助期的成功：a）人类报告基因构建将被开发和用于研究 更好地理解患者过继性T细胞治疗中T细胞相互作用和活化，（项目1 和2），和B）与评估药物治疗反应相关的关键分子的分子成像， 特别是用于信号转导抑制剂，尤其是在实体瘤中（项目3-5）。报告基因 过继性细胞治疗中的成像应用，包括靶向CD 4和CDS亚型以及嵌合T细胞 与T细胞与人工反应性前列腺癌，将研究在人类使用人类衍生的 报告基因（P1和P2）：EB病毒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; O 'Rielly，共同领导人），以及PET成像的生存，激活， 对遗传重定向的前列腺特异性T细胞的细胞因子刺激的应答（V. Ponomarev，项目2 leader; M. Sadelain，共同领导人）。在项目3中，高场MRI/MRS将探测体内 药物转化和代谢，以预测对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物（J. Koutcher，项目3负责人）。在项目4和5中，Positron 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，使用雄激素受体，her 2和热休克蛋白90的新型放射性配体。的 新的信号转导抑制剂作用的体内成像方法学的发展 翻译到诊所（N。罗森，项目3负责人; Solit，共同领导人），以及 去势抵抗性转移性前列腺癌（S. Larson，Project 5 leader; H. Scherand P. Smith-Jones，coleaders）. 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，新的分子成像范例将用于解决重要的临床问题， 肿瘤学

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 androgen 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. Scherand 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.