Antibody Targeted Radiation and Immunotherapy for the Treatment of Solid Tumors

描述(申请人提供)：这是我们计划项目资助的第三次竞争性续签。我们修改了名称，以反映在病灶、抗体靶向放射和免疫治疗实体肿瘤治疗方面的改进。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单抗预靶向治疗，3)CEA靶向免疫治疗 项目1利用了我们为实体肿瘤的RIT开发的最有效的策略，在最合适的临床环境下将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次PPG的合成化学工作合并为一个项目，该项目现在显然专注于开发临床适用的预靶向方法。项目3是我们在设计抗CEA-IL2免疫细胞因子的基础上发展出来的一个新项目。这些项目将得到同样的六个核心(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，这些核心一直是研究和临床试验的基础。这一应用领域新增了一批关键人员：Colcher博士拥有超过25年的克隆抗体研究经验，Yu博士拥有世界知名的分子免疫学专业知识，Radany博士拥有超过25年的放射生物学临床和研究经验，Bding博士拥有超过25年的成像物理学经验，Frankel博士提供出色的生物统计学支持，Hudson博士致力于新型构建技术，我们的合作者Conti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且必不可少的：蛋白质工程的吉利斯博士，螯合化学和抗螯合抗体的米尔斯博士，以及在免疫学方面的卓越专业知识的赖斯菲尔德博士。这一应用还因使用了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、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、用于发现新结构的高通量筛查、获得许可的符合cGMP的生物生产设施，以及新成立的由Kalos博士领导的临床免疫学相关支持实验室。这一切都是在新成立的癌症免疫治疗和肿瘤免疫学部的背景下进行的，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，该设施将容纳计划项目团队的大部分成员。

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.