Core A: Administrative and Clinical Translational Core

摘要核心A：行政和临床翻译核心 此更新计划项目的管理和临床翻译核心将提供：(1)科学 和临床业务监督；(2)支持IND的监管和临床开发专业知识；以及 生物统计和预算结构，以支持每个P01项目和科学核心的有效运作； (3)促进项目整合和协同。这项续订建议寻求在我们已证实的轨道基础上再接再厉 通过增强嵌合抗原受体T细胞平台进行基因工程T细胞治疗的记录 具体解决我们迄今在临床试验中观察到的系统性脆弱性。我们的 最重要的假设是，新的基因编辑方法可以消除道路上剩余的障碍 无处不在的、普遍有效的CAR T细胞疗法治疗血液系统恶性肿瘤。我们有 汇集了一批杰出的研究人员，他们合作并共同发表了许多 好几年了。每个以疾病为重点的项目都将由该领域公认的权威机构领导。这三个核心 到目前为止，支持这项提议对我们的临床CAR T细胞计划的成功和他们的 专业知识将为这项提议的成功奠定基础。每个项目的核心都是一个创新的临床 寻求检验我们的主要假设的试验。 我们正在利用成熟的翻译基础设施、管理人员和集中化的研究 佩雷尔曼医学院细胞免疫治疗中心的组织来实现我们的 目标。来自艾布拉姆森癌症中心、佩雷尔曼医学院的坚定机构承诺， 帕克癌症免疫治疗研究所和宾夕法尼亚大学促进了我们的 科学和翻译成果。核心A提供的基本服务包括行政管理 为每个项目和核心中的所有调查员提供支助；财政管理和监督 计划项目；临床方案开发、IND提交和维护，以及临床数据 管理；组织和沟通所有计划项目会议和活动。整体而言 这个核心的目标是有效和高效地领导P01。主任、联合调查员的角色 而行政人员则是在促进沟通和组织结构的同时，激发科学的 和技术互动。为了实现这一目标，核心确定了四个目标：(1) 监督宾夕法尼亚大学和CHOP临床站点的安全和监测活动；(2)提供监管， 临床前开发，以及对临床试验、项目和核心的统计支持以及实施数据 共享计划；(3)协调临床医生和科学家在项目和核心、内部 和外部咨询委员会，以及NCI人员关于有效实施拟议目标的建议； (4)提供费用跟踪、提供调查人员月报等预算服务。

SUMMARY CORE A: ADMINISTRATIVE AND CLINICAL TRANSLATIONAL CORE The Administrative and Clinical Translational Core of this renewal Program Project will provide: (1) scientific and clinical operational oversight; (2) IND-enabling regulatory and clinical development expertise, and biostatistical and budgetary structure to support effective operations for each P01 Project and Scientific Core; and (3) promote project integration and synergy. This renewal proposal seeks to build upon our proven track record in genetically engineered T cell therapy by enhancing the chimeric antigen receptor T cell platform to specifically address systemic vulnerabilities that we have observed in our clinical trials to date. Our overarching hypothesis is that novel gene editing approaches can remove the remaining obstacles in the path of universally-available and universally-active CAR T cell therapy for hematologic malignancy. We have brought together a cadre of exceptional investigators who have collaborated and published together for many years. Each disease-focused project will be led by a recognized authority in the field. The three cores that support this proposal have been critical to the success of our clinical CAR T cell program to date and their expertise will underpin the success of this proposal. The centerpiece of each project is an innovative clinical trial that seeks to test our major hypotheses. We are leveraging the proven translational infrastructure, administrative staff and the centralized research organizations at the Center for Cellular Immunotherapies at the Perelman School of Medicine to achieve our objectives. Strong institutional commitment from the Abramson Cancer Center, Perelman School of Medicine, the Parker Institute for Cancer Immunotherapy and the University of Pennsylvania have facilitated our scientific and translational achievements. The essential services provided by Core A include administrative support for all investigators in each project and core; fiscal management and oversight for all components of the Program Project; clinical protocol development, IND submissions and maintenance, and clinical data management; and organization and communication of all Program Project meetings and activities. The overall goal of this Core is effective and efficient leadership of the P01. The roles of the Director, Co-investigators and administrative staff are to facilitate communication and organizational structure while stimulating scientific and technological interactions. In order to achieve this goal, the Core has established four objectives: (1) To oversee the safety and monitoring activities for Penn and CHOP clinical sites; (2) To provide regulatory, preclinical development, and statistical support for clinical trials, projects and cores and implement data sharing plans.; (3) To coordinate the interactions among clinicians and scientists in projects and cores, internal and external advisory boards, and NCI personnel regarding effective implementation of proposed objective; (4) To provide budgetary services such as tracking expenses and providing investigator’s monthly reports.