SPORE in Skin Cancer

皮肤癌中的孢子

• 批准号: 8548580
• 负责人: John Munn Kirkwood
• 金额: $ 215.05万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-26 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8548580
• 关键词: Adjuvant; Adjuvant Study; Adjuvant Therapy; Adverse effects; Antigens; Apoptotic; BRAF gene; Bioinformatics; Biological Assay; Biological Markers; Biology; Biometry; Biostatistics Core; Blocking Antibodies; CTLA4 gene; Cancer Burden; Cancer Patient; Cell Death; Clinical; Clinical Research; Combined Modality Therapy; Communities; Cutaneous; Cutaneous Melanoma; Data; Data Analyses; Dendritic Cell Vaccine; Dermatology; Development; Disease; Dose; Eastern Cooperative Oncology Group; Engineering; Faculty; Funding; Genes; Genetic; Genomics; Goals; Housing; Immune; Immune response; Immunization; Immunologic Monitoring; Immunologics; Immunology; Immunosuppression; Immunotherapeutic agent; Immunotherapy; In Situ; Incidence; Individual; Inflammation; Inflammatory Response; Informatics; Interferon-alpha; Interferons; International; Laboratories; Length; Machine Learning; Metastatic Melanoma; Modality; Molecular; Monitor; Organ; Outcome; Pathway interactions; Patients; Phase; Predictive Value; Process; Proteomics; Recurrence; Relapse; Research; Research Infrastructure; Research Personnel; Resource Informatics; Resources; Risk; Role; Safety; Skin Cancer; Skin Carcinoma; Specialized Program of Research Excellence; Survival Rate; T-Cell Lymphoma; T-Lymphocyte; Technology; Testing; Therapeutic; Tissue Banking; Tissue Banks; Translational Research; Translations; Treatment outcome; Tumor Immunity; University of Pittsburgh Cancer Institute; Unresectable; Vaccination; Vaccines; Viral Vector; base; career development; chemotherapeutic agent; data management; design; dosage; effective therapy; high risk; immunogenic; immunogenicity; improved; in vivo; inflammatory marker; inhibitor/antagonist; melanoma; new technology; novel; novel therapeutics; novel vaccines; oncology; pre-clinical; prevent; prognostic; programs; research and development; response; therapeutic target; tumor; tumor progression

The incidence of melanoma has risen dramatically in recent years, but no therapy has improved overall survival for the majority of patients with unresectable metastatic disease. The University of Pittsburgh Cancer Institute (UPCI) Melanoma and Skin Cancer Program (MSCP) will continue to conduct a Specialized Program of Research Excellence (SPORE) to improve our understanding of molecular and immunologic mechanisms of cancer progression and to validate prognostic and predictive biomarkers for personalized treatment of advanced melanoma and cutaneous T cell lymphoma (CTCL). Of our 4 Projects, 1 is continued from the prior funding period, and 3 new projects have been derived from developmental research conducted in the last period; 1 of the prior SPORE projects will be continued with independent ROI funding. Our highly integrated approach leverages complementary expertise in melanoma, oncology, dermatology, immunology, biostatistics, bioinformatics, machine learning, genomics, proteomics, and biomarker discovery to test hypotheses central to the improvement of therapeutic outcome in skin cancers. Regardless of clinical outcomes, these Projects will also generate urgently needed mechanistic data to inform development of new therapeutic strategies and pathways through which to monitor relapse and progression. Our 4 Projects will evaluate: (1) the prognostic and predictive value of the pro-inflammatory response and markers of immune suppression in relation to ipilimumab and interferon (IFN)¿ adjuvant therapy (leveraging an Eastern Cooperative Oncology Group-led adjuvant trial); (2) an engineered, 3-antigen dendritic cell vaccine and IFN¿ boost in patients with metastatic melanoma; (3) the safety and efficacy of vemurafenib modulation of immunotherapy with IFN¿2b in patients with metastatic melanoma; and (4) an entirely new personalized microneedle vaccination technology in patients with melanoma and CTCL. The Administrative Core (A) coordinates the clinical research and provides scientific and fiscal oversight of the entire SPORE. The Biospecimen Core (B) is housed in the UPCI Immunologic Monitoring and Cellular Products Laboratory, where all tissue banking, biospecimen processing, and immune assays are conducted. The Biostatistics Core (C) and Informatics Core (D) support all projects with data analysis and management, respectively. We will continue to solicit, review, and fund applications for the career development and developmental research programs, which in the prior funding period led to the design of a new full project in this application (Project 3) and the promotion of career development recipients to co-investigators and a project leader.

近年来，黑色素瘤的发病率急剧上升，但没有任何治疗方法能提高大多数不能切除的转移性疾病患者的总体存活率。匹兹堡大学癌症研究所(UPCI)黑色素瘤和皮肤癌项目(MSCP)将继续实施一项专门的卓越研究项目(SPORT)，以提高我们对癌症进展的分子和免疫学机制的理解，并验证用于个体化治疗晚期黑色素瘤和皮肤T细胞淋巴瘤(CTCL)的预后和预测生物标记物。在我们的4个项目中，1个是从上一个资助期继续进行的，3个新项目是从上一个资助期进行的开发研究得出的；1个先前的孢子项目将继续使用独立的ROI资金。我们的高度集成方法利用黑色素瘤、肿瘤学、皮肤病学、免疫学、生物统计学、生物信息学、机器学习、基因组学、蛋白质组学和生物标记物发现方面的互补专业知识来测试对改善皮肤癌治疗结果至关重要的假设。无论临床结果如何，这些项目还将产生迫切需要的机械性数据，以便为开发新的治疗战略和途径提供信息，通过这些战略和途径监测复发和进展。我们的四个项目将评估：(1)与ipilimumab和干扰素(干扰素)辅助治疗相关的促炎反应和免疫抑制标志物的预后和预测价值(利用东方合作肿瘤小组主导的辅助试验)；(2)针对转移性黑色素瘤患者的基因工程3抗原树突状细胞疫苗和干扰素增强治疗；(3)维莫拉非尼调节干扰素2b对转移性黑色素瘤患者免疫治疗的安全性和有效性；以及(4)针对黑色素瘤和CTCL患者的全新个性化微针接种技术。管理核心(A)协调临床研究，并提供对整个孢子的科学和财政监督。Biospecimen Core(B)设在UPCI免疫监测和细胞产品实验室，所有的组织库、生物Specimen处理和免疫分析都在这里进行。生物统计核心(C)和信息学核心(D)分别为所有项目提供数据分析和管理支持。我们将继续征集、审查和资助职业发展和发展研究计划的申请，这些申请在上一次资助期间导致了本次申请中新的完整项目的设计(项目3) 以及将职业发展获得者提升为合作调查员和项目负责人。