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 im...