Antibody Targeted Radiation and Immunotherapy for the Treatment of Solid Tumors

描述（由申请人提供）：这是我们的计划项目补助金的第三次竞争性更新。我们已经修改了名称，以反映重点的细化，抗体靶向放射和免疫疗法治疗实体瘤。有三个项目，1）放射免疫治疗：临床和放射生物学研究，2）抗cea单克隆抗体的预靶向治疗，3）cea靶向免疫治疗 项目1利用了我们为实体瘤RIT开发的最有效的策略，在最合适的临床环境中将RIT与化疗相结合。重要的是增加了放射生物学研究部分。项目2是将我们的抗体工程工作和上一个PPG的合成化学工作合并为一个项目，该项目现在明确侧重于开发临床适用的预靶向方法。项目3代表了一个新的项目，它是从我们以前的工程化抗CEA-IL 2免疫细胞因子的工作中发展出来的。这些项目将得到相同的六个核心（临床成像，放射性药物，临床生产，动物核心，生物统计学和管理）的支持，这些核心是研究和临床试验的基础。这份申请书上有一些新的关键人员; Colcher博士拥有超过25年的单克隆抗体经验，Yu博士拥有世界知名的分子免疫学专业知识，Radany博士对放射生物学具有临床和研究兴趣，Bading博士拥有超过25年的成像物理学，Frankel博士提供出色的生物统计学支持，哈德逊博士提供新型结构，我们的合作者康迪博士提供临床成像方面的专业知识。我们的外部合作者是杰出的和必不可少的;吉利斯博士的蛋白质工程，Meares博士的螯合物化学和抗螯合物抗体和Reisfeld博士在免疫学方面的巨大专业知识。这一应用还因其使用尖端技术而引人注目;用于免疫治疗项目的CEA转基因小鼠，分子靶向免疫治疗剂，用于动物和临床研究的先进成像，用于放射增敏和免疫治疗的纳米颗粒，用于发现新构建体的高通量筛选，获得许可的cGMP合规生物制剂生产设施，以及由Kalos博士领导的新成立的临床免疫学相关支持实验室。这一切都发生在新成立的癌症免疫治疗和肿瘤免疫学部门的背景下，希望之城承诺在2008年夏天之前建造一个新的6000万美元的设施，该设施将容纳大部分计划项目团队。

DESCRIPTION (provided by applicant): This is the third competitive renewal of our Program Project Grant. We have modified the name to reflect the refinement in focus, Antibody Targeted Radiation and Immunotherapy for the Treatment of Solid Tumors. There are three projects, 1) Radioimmunotherapy: clinical and radiobiologic studies, 2) pretargeting with anti-cea mabs for therapy, and 3) cea-targeted immunotherapeutics Project 1 exploits the most effective strategies we have developed for RIT of solid tumors, combining RIT with chemotherapy in the most appropriate clinical setting. Significant is the addition of a radiobiologic research component. Project 2 is a merger of our antibody engineering effort and the synthetic chemistry effort from the last PPG into a project which now clearly focuses on the development of clinically applicable pretargeting approaches. Project 3 represents a new project which has developed out of our previous work on engineering an anti-CEA-IL2 immunocytokine. The projects will be supported by the same six cores (Clinical Imaging, Radiopharmacy, Clinical Production, Animal Core, Biostatistics, and Administration) that have been the foundation for both the research and the clinical trials. There are a number of new key personnel on this application; Dr. Colcher, with over 25 years of experience with monoclonal antibodies, Dr. Yu with world renown expertise in molecular immunology, Dr. Radany with both clinical and research interests in radiobiology, Dr. Bading with over 25 years of imaging physics, Dr. Frankel providing excellent biostatistical support, Dr. Hudson for novel constructs, and our collaborator Dr. Conti providing expertise in clinical imaging. Our outside collaborators are outstanding and essential; Dr. Gillies for protein engineering, Dr. Meares for chelate chemistry and anti-chelate antibodies and Dr. Reisfeld for his tremendous expertise in immunology. This application is also notable for its use of cutting edge technologies; CEA transgenic mice for the immunotherapy projects, molecularly targeted immunotherapeutics, advanced imaging for both animal and clinical studies, nanoparticles for both radiosensitization and immunotherapy, high throughput screening to discover new constructs, a licensed cGMP compliant biologies production facility, and the newly established Clinical Immunology Correlates Support Laboratory headed by Dr. Kalos. This is all taking place in the setting of the newly established Division of Cancer Immunotherapeutics & Tumor Immunology, with a commitment from the City of Hope to build a new $60M facility by summer 2008 which will house most of the Program Project Team.