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.

Public Health Relevance

The RPCI-UPCI Ovarian Cancer SPORE is relevant to the public health because each of the projects will have a direct impact on risk assessment, prognostic classification or targeted therapy for prevention and treatment of primary or recurrent disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA159981-02
Application #
8737201
Study Section
Special Emphasis Panel (ZCA1-RPRB-M (J1))
Program Officer
Arnold, Julia T
Project Start
2013-09-18
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$2,162,000
Indirect Cost
$554,970
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Danaher, Patrick; Warren, Sarah; Dennis, Lucas et al. (2017) Gene expression markers of Tumor Infiltrating Leukocytes. J Immunother Cancer 5:18
Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A et al. (2017) History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium. Cancer Causes Control 28:469-486
Ovarian Tumor Tissue Analysis (OTTA) Consortium (2017) Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer. JAMA Oncol 3:e173290
Minlikeeva, Albina N; Freudenheim, Jo L; Cannioto, Rikki A et al. (2017) History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report. Br J Cancer 117:1063-1069
Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan et al. (2017) Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. Br J Cancer 116:524-535
Eng, Kevin H; Morrell, Kayla; Starbuck, Kristen et al. (2017) Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer. Gynecol Oncol 146:52-57
Dicks, Ed; Song, Honglin; Ramus, Susan J et al. (2017) Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene. Oncotarget 8:50930-50940
Huang, Ruea-Yea; Francois, Ariel; McGray, Aj Robert et al. (2017) Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer. Oncoimmunology 6:e1249561
Szender, J Brian; Papanicolau-Sengos, Antonios; Eng, Kevin H et al. (2017) NY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer. Gynecol Oncol 145:420-425
Grabosch, Shannon; Tseng, George; Edwards, Robert P et al. (2017) Multiplex profiling identifies distinct local and systemic alterations during intraperitoneal chemotherapy for ovarian cancer: An NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol 146:137-145

Showing the most recent 10 out of 105 publications