Roswell Park Ovarian Cancer SPORE

罗斯威尔公园卵巢癌孢子

• 批准号: 10171142
• 负责人: KIRSTEN B. MOYSICH
• 金额: $ 171.61万
• 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 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10171142
• 关键词: Address; Advocate; Award; Basic Science; Bioinformatics; Biological Markers; Biometry; Bypass; CD8-Positive T-Lymphocytes; CTAG1 gene; CXCR4 gene; Cancer Patient; Cancer Research Project; Cessation of life; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Collaborations; Communities; Data; Dendritic Cells; Development; Discipline; Disease; Engineering; Ensure; Environment; Epithelial ovarian cancer; Extramural Activities; Fostering; Funding; Future; Genes; Goals; Human; Immune; Immune mediated destruction; Immune response; Immune system; Immunogenomics; Immunologics; Immunosuppression; Immunotherapy; Incubators; Individual; Infiltration; Institution; Investigation; K-Series Research Career Programs; Laboratories; Malignant neoplasm of ovary; Mentors; Myeloid-derived suppressor cells; Nature; Oncolytic viruses; Outcome; PD-L1 blockade; Pathology; Patient-Focused Outcomes; Patients; Phase I/II Clinical Trial; Pilot Projects; Play; Prevention; Productivity; Prognosis; Property; Randomized; Recurrence; Research; Research Personnel; Research Project Grants; Resource Sharing; Resources; Role; Scientist; Surgical Management; T cell therapy; T-Lymphocyte; Testing; Therapeutic; Transforming Growth Factor beta; Transgenic Organisms; Translational Research; Translations; Tumor Antigens; Tumor Escape; Tumor Immunity; Tumor Tissue; Tumor-infiltrating immune cells; Vaccination; Woman; anticancer research; base; cancer cell; career; clinical practice; disorder control; exhaustion; first-in-human; high risk; immune checkpoint blockade; immune resistance; improved; improved outcome; in vivo; innovation; innovative technologies; inter-institutional; interest; macrophage; multidisciplinary; novel; novel marker; novel strategies; organizational structure; ovarian neoplasm; patient engagement; pre-clinical; programs; proteogenomics; recruit; resistance mechanism; response; success; therapeutic effectiveness; translational cancer research; translational impact; translational research program; translational study; tumor

Overall Summary – Roswell Park Ovarian Cancer SPORE This is the revised competing renewal application of the Roswell Park Ovarian Cancer SPORE. We have made significant progress on the translational objectives and human endpoints of each Individual Research Project (IRP). Our highly successful Developmental Research Program (DRP) and Career Enhancement Program (CEP) have catalyzed new translational ovarian cancer research projects, collaborations, and extramural funding for awardees. Our overarching goal remains unchanged: to conduct multidisciplinary, mechanism-based and collaborative translational research that will have the highest possible impact for women with ovarian cancer. Because immunotherapies have met with only modest success in ovarian cancer patients, we continue to uniquely focus on novel strategies for generating effective anti-tumor immunity by unraveling immune-resistance mechanisms and identifying novel proteogenomic biomarkers of responsiveness. After significant planning and guidance by our Internal and External Advisory Boards, and Patient Advocate Committee, we have leveraged our highly successful DRP and CEP to propose three bi-directional translational IRPs addressing basic and clinical research questions of importance in ovarian cancer. The new IRP1 and IRP2 evolved as a result of two DRP awards and the new IRP3 developed from a CEP award. IRP1 will test an oncolytic virus armed with a CXCR4 antagonist in combination with PDL1 blockade to abrogate tumor immune suppression and limit T cell exhaustion in a randomized Phase I/II clinical trial. IRP2 will test a novel strategy of rendering NY-ESO-1-reactive TCR transgenic T cells to be insensitive to the suppressive action of TGF and concomitantly neutralize M2- macrophages/myeloid-derived suppressor cells. IRP3 addresses the completely novel concept of identifying mismatch between immunopeptidomes of ovarian cancer cells versus dendritic cells and leveraging a computational approach of bypassing such mismatch. IRP1 commences with a planned clinical trial; the Phase I/II clinical trials in IRP2 and IRP3 will commence in year 3 following preclinical, IND-enabling translational studies. The program also continues to expand opportunities for new avenues of ovarian cancer translational research via its successful DRP and CEP. The four highly integrated, interconnected shared resource cores – Administration, Biospecimen & Pathology, Biostatistics & Bioinformatics, and Immunogenomics – bring innovative technology and resources to the SPORE and do not duplicate pre-existing shared resources available at Roswell Park. This application is strongly supported by nearly $4M institutional commitment to ensure its success of conducting highly innovative translational research that changes the clinical practice paradigm in ovarian cancer.

卵巢癌的早期症状有哪些？ 这是罗斯威尔公园卵巢癌孢子的修订竞争更新申请。我们取得了 在每个单独研究项目的转化目标和人类终点方面取得重大进展 （IRP）。我们非常成功的发展研究计划（DRP）和职业提升计划（CEP） 已经催化了新的转化卵巢癌研究项目，合作和校外资金， 获奖者我们的总体目标保持不变：开展多学科、基于机制和 合作转化研究，这将对卵巢癌妇女产生最大可能的影响。 由于免疫疗法在卵巢癌患者中仅取得了适度的成功，我们将继续 独特地专注于通过解开免疫抗性产生有效的抗肿瘤免疫的新策略 机制和识别新的反应性蛋白基因组生物标志物。经过大量的规划和 在我们的内部和外部咨询委员会以及患者倡导委员会的指导下，我们利用了 我们非常成功的DRP和CEP提出了三个双向翻译IRP解决基本和 卵巢癌临床研究的重要问题。新的IRP1和IRP2是由两个 DRP奖项和新的IRP 3从CEP奖项发展而来。IRP1将测试一种溶瘤病毒， CXCR4拮抗剂与PDL1阻断剂联合用于消除肿瘤免疫抑制并限制T细胞 在一项随机I/II期临床试验中，IRP2将测试一种使NY-ESO-1具有反应性的新策略 TCR转基因T细胞对TGF β 1的抑制作用不敏感，同时中和M2- 巨噬细胞/髓源性抑制细胞。IRP 3提出了全新的识别概念 卵巢癌细胞与树突状细胞的免疫肽段之间的错配， 绕过这种失配的计算方法。IRP 1开始计划临床试验;阶段 IRP 2和IRP 3的I/II期临床试验将在临床前、IND使能转化后的第3年开始 问题研究该计划还将继续扩大卵巢癌转化的新途径的机会 通过其成功的DRP和CEP进行研究。四个高度集成、互联互通的共享资源核心- 管理学、生物标本与病理学、生物统计学与生物信息学和免疫基因组学-带来 创新技术和资源，不重复现有的共享资源 在罗斯威尔公园这项申请得到了近400万美元的机构承诺的大力支持，以确保其 成功进行高度创新的转化研究，改变临床实践范式， 卵巢癌