RPCI-UPCI Ovarian Cancer SPORE

RPCI-UPCI 卵巢癌孢子

• 批准号: 9111874
• 负责人: KUNLE O. ODUNSI
• 金额: $ 41.18万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111874
• 关键词: Address; Antigens; Area; Autologous; Avidity; Biological Markers; Biometry; CD8B1 gene; Cancer Patient; Cancer Prognosis; Cells; Classification; Clinical Research; Clinical Trials; Collaborations; Communities; Data; Dendritic Cells; Development; Diagnosis; Dioxygenases; Discipline; Disease Marker; Disease remission; Environment; Enzymes; Epithelial ovarian cancer; Etiology; Fostering; Generations; Goals; Guidelines; Histologic; Immune; Immune Tolerance; Immune system; Immunity; Immunologic Monitoring; Immunosuppressive Agents; Individual; Infiltration; Investigation; K-Series Research Career Programs; Lead; Lymphocyte; MHC Class I Genes; Malignant Neoplasms; Malignant neoplasm of ovary; Mediating; Medical Informatics; Memory; Mentors; Meta-Analysis; Morbidity - disease rate; Myelogenous; Operative Surgical Procedures; Outcome; Participant; Pathway interactions; Patients; Pilot Projects; Predictive Value; Prevention; Property; Public Health; Recruitment Activity; Recurrence; Recurrent disease; Regimen; Relapse; Research; Research Personnel; Research Project Grants; Resistance; Resources; Risk; Risk Assessment; Roswell Park Cancer Institute; Scientist; Staging; Suppressor-Effector T-Lymphocytes; T cell therapy; T-Lymphocyte; Testing; Therapeutic; Training; Translational Research; Translational Research Working Group; Translations; Tryptophan 2,3 Dioxygenase; Tumor Burden; Universities; University of Pittsburgh Cancer Institute; Vaccines; Woman; anticancer research; base; cancer therapy; career; career development; chemotherapy; clinical practice; combinatorial; conditioning; design; high risk; improved; improved outcome; indoleamine; inhibitor/antagonist; innovation; inter-institutional; interest; intraepithelial; mTOR inhibition; mortality; novel; novel marker; novel strategies; novel therapeutics; outcome forecast; ovarian cancer prevention; ovarian neoplasm; population based; prognostic; programs; public health relevance; research and development; response; targeted treatment; therapeutic biomarker; treatment stratification; tumor; vaccine efficacy

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.

描述（由申请人提供）：罗斯威尔公园癌症研究所（RPCI）和匹兹堡大学（UPCI）卵巢癌孢子的总体目标是通过创新的转化研究降低卵巢癌的发病率和死亡率。它包括四个单独的研究项目，四个支持核心，以及研究和职业发展计划。该提案汇集了基础和应用研究人员，以进行创新和多样化的翻译研究，旨在进行风险分层，治疗， 原发性和复发性卵巢癌，并预防缓解期患者复发。这四个项目经过精心设计，具有在五年内改变卵巢癌临床实践模式的巨大潜力。该计划的主题独特地反映了卵巢癌患者病因、预后和治疗方面基于免疫的方法。拟议的项目将：1）测试一种新的治疗策略，以打破卵巢癌中吲哚胺2，3-双加氧酶（IDO）介导的免疫耐受，同时在第二次缓解的患者中诱导抗肿瘤特异性免疫2）测试mTOR抑制和IL-21的组合策略，用于抗原刺激的CD 8 + T细胞的离体调节以获得效应子和记忆功能属性;并在临床试验中测试离体产生的细胞是否产生针对卵巢肿瘤的持久免疫力3）测试自体肿瘤负载的1型极化树突状细胞（DC 1）是否会产生能够以MHC I类限制性或MHC I类非限制性方式识别卵巢癌的CTL;当用作疫苗和过继性T细胞治疗时（项目3）;确定髓源性抑制细胞（MDSC）的预测意义，其在卵巢癌患者的长期存活中具有强免疫抑制特性（项目4）。每个项目至少涉及SPORE指南中概述的一个翻译领域，并且该计划涉及翻译研究工作组定义的翻译途径。四个核心将支持这些项目：管理，生物标本，生物统计学和医学信息学，免疫监测。发展研究计划将支持一条途径，继续识别和支持可以取代或改进当前项目的各种研究，职业发展计划将招募和支持致力于卵巢癌转化研究培训的候选人。发展研究计划和职业发展计划将提供一个框架，指导年轻的研究人员在卵巢癌转化研究中发展职业生涯，并对具有转化潜力的高风险，潜在范式改变项目进行施肥测试。