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可以改善大多数无法切除的转移性疾病患者的总体生存率。匹兹堡大学癌症研究所 (UPCI) 黑色素瘤和皮肤癌项目 (MSCP) 将继续开展一项研究。卓越研究专门计划 (SPORE) 旨在提高我们对癌症进展的分子和免疫机制的理解，并验证晚期黑色素瘤和皮肤 T 细胞淋巴瘤 (CTCL) 个性化治疗的预后和预测生物标志物。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中衍生出来的；其中 1 个之前的 SPORE 项目将在独立的 ROI 资助下继续进行，我们的高度集成的方法利用了黑色素瘤领域的互补专业知识。 、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志物发现，以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。还将产生急需的机制数据，为开发新的治疗策略和途径提供信息，以监测复发和进展。我们的 4 个项目将评估：（1）促炎症反应和免疫抑制标志物的预后和预测价值。与易普利姆玛和干扰素 (IFN) 的关系¿辅助治疗（利用东部肿瘤合作组主导的辅助试验）；(2) 工程化 3 抗原树突状细胞疫苗和 IFN¿增强转移性黑色素瘤患者的疗效；(3) 威罗非尼 (vemurafenib) 调节 IFN 免疫疗法的安全性和有效性2b 针对转移性黑色素瘤患者；(4) 针对黑色素瘤和 CTCL 患者的全新个性化微针疫苗接种技术。 B) 位于 UPCI 免疫监测和细胞产品实验室，所有组织库、生物样本处理和免疫分析均在此进行。信息学核心（D）分别支持所有数据分析和管理项目，我们将继续征求、审查和资助职业发展和发展研究项目的申请，这些项目在之前的资助期间导致了新的完整项目的设计。本应用程序中的项目（项目 3） 将职业发展接受者晋升为共同研究者和项目负责人。