The proposed Center for Immunotherapeutic Transport Oncophysics (CITO) is focused on identifying and understanding the multi-scale transport properties of immune cells and molecules, both systemically and within the tumor microenvironment, and other specific biological and physical properties of the tumor microenvironment, to ultimately develop effective cancer immunotherapies. The major CITO components are summarized as follows. Project 1 proposes to determine the transport phenomena of dendritic cell (DC) vaccines for breast and pancreatic cancers and post-vaccination changes in the transport of endogenous DCs, effector T cells, and macromolecular drugs. This information will be used to improve immune responses in these two cancer models. Project 2 seeks to determine the effects of multi-scale transport phenomena of pancreatic ductal adenocarcinoma (PDAC) on the distribution of immune cells and nutrients in the tumor microenvironment, during tumor progression. The Transport Oncophysics Core (TOC) will support both projects with modeling, computational, and imaging capabilities to integrate the scientific data into parameters that ultimately inform the rational design of optimal cancer immunotherapeutics and to improve the immunogenicity of breast and pancreatic cancers, both of which are historically known to be lowly immunogenic. The Education and Outreach Unit (EOU) will serve as the communication and engagement platform for students, trainees, junior faculty investigators, and researchers of the CITO, and those of the Physical Sciences-Oncology Network (PS-ON) and beyond. The Administrative Core (AC) will be established as part of the CITO infrastructure through which the Principal Investigator (PI), Project Co-Leaders and Core Leader, researchers, trainees, advisors, NCI PS-ON program staff, and other scientific and patient communities can share information and synergize CITO-related activities. The AC will facilitate the accomplishment and evaluation of progress and the creation of a collaborative network for current and future scientists in physical sciences oncology. The AC will also oversee and manage the selection and funding of Pilot and Trans-Network Projects, coordinate the use of shared resources and facilities, and promote interaction with other PS-ON investigators. Dr. Mauro Ferrari (Center PI, senior physical sciences investigator, AC Co-Leader, TOC Leader; Houston Methodist Research Institute, HMRI) will serve as the AC Co-Leader (10% effort). Dr. Elizabeth Mittendorf (Center cancer clinical translation investigator; AC Co-Leader; Project 1 Co-Leader; MD Anderson Cancer Center), Dr. Rongfu Wang (Center senior cancer immunology investigator; AC Co-Leader; Project 1 Co-Leader; HMRI), and Dr. Rolf Brekken (senior cancer biology investigator; AC Co- Leader; Project 2 Co-Leader; UT Southwestern Medical Center) will also serve as the other three AC Co- Leaders (5% effort each in the AC). They will be supported by a Center Administrator and staff.
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