RPCI-UPCI Ovarian Cancer SPORE

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DESCRIPTION (provided by applicant): The overall goal of the University of the Roswell Park Cancer Institute (RPCI) and University of Pittsburgh (UPCI) Ovarian Cancer SPORE is to reduce the morbidity and mortality of ovarian cancer through innovative translational research. It includes four individual research projects, four supportive cores, and research and career development programs. This proposal brings together basic and applied investigators to conduct innovative and diverse translational investigations aimed at risk stratification, treatment of primary and recurrent ovarian cancer, and prevention of relapse in patients in remission. The four projects have been carefully designed to have significant potential to change clinical practice paradigms in ovarian cancer within five years. The theme of the program uniquely reflects immune based approaches in the etiology, prognosis and treatment of patients with ovarian cancer. The proposed projects will: 1) Test a novel therapeutic strategy to break indoleamine 2,3-dioxygenase (IDO)-mediated immune tolerance in ovarian cancer, while inducing anti-tumor-specific immunity in patients in second remission (Project 1); 2) Test a combinatorial strategy of mTOR inhibition and IL-21 for ex-vivo conditioning of antigen stimulated CD8+ T cells for effector and memory functional attributes; and test whether the ex vivo generated cells produce durable immunity against ovarian tumor in a clinical trial (Project 2); 3) Test whether autologous tumor-loaded type-1-polarized dendritic cells (¿DC1s) will generate CTLs capable of recognizing ovarian cancer in either MHC class I-restricted- or MHC class l-unrestricted fashion; when used both as a vaccine and for adoptive T cell therapy (Project 3); Determine the predictive significance of myeloid derived suppressor cells (MDSCs), which have strong immunosuppressive properties in the long term survival of ovarian cancer patients (Project 4). Each project addresses at least one of the translational areas outlined in the SPORE guidelines and together, the program addresses the translational pathways defined by the Translational Research Working Group. Four Cores will support these projects: Administration, Biospecimen, Biostatistics and Medical Informatics, Immune Monitoring. The Developmental Research Program will support a pathway for continued identification and support of diverse research that could replace or improve current projects, and a Career Development Program will recruit and support candidates committed to training in translational research in ovarian cancer. The Developmental Research Program and the Career Developmental Program will provide a framework to mentor young investigators to develop careers in ovarian cancer translational research, and to fertilize testing of high risk, potentiall paradigm changing projects with translational potential.