Moffitt Skin Cancer SPORE

莫菲特皮肤癌孢子

• 批准号: 8548784
• 负责人: Jeffrey S Weber
• 金额: $ 167.28万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8548784
• 关键词: Achievement; Adoptive Immunotherapy; BRAF gene; Basal Cell Cancer; Biohazardous Substance; Bioinformatics; Biological Assay; Biological Markers; Biology; Biometry; Biostatistics Core; Budgets; Cancer Center; Cancer Patient; Cells; Clinic; Clinical; Clinical Trials; Collaborations; Comprehensive Cancer Center; Country; Critiques; Cutaneous; Cutaneous Melanoma; Cytotoxic agent; Data; Dermatology; Development; Discipline; Epidemiology; Epigenetic Process; Equine mule; Faculty; Goals; Hematology; Histones; Human Papilloma Virus Vaccine; Human Papillomavirus; Immune; Immunity; Immunology; Immunotherapy; Individual; Investigation; Laboratories; Lead; Malignant Neoplasms; Merkel Cells; Metastatic Melanoma; Metastatic/Recurrent; Modality; Movement; Mutate; Papillomavirus Infections; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phase II/III Trial; Phase III Clinical Trials; Play; Polyomavirus; Polyomavirus Infections; Pongidae; Prevention; Preventive Intervention; Prospective Studies; Randomized; Recommendation; Relapse; Reproduction spores; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resected; Resistance; Resources; Scientist; Signal Transduction; Skin; Skin Cancer; Skin Carcinoma; Specimen; Squamous cell carcinoma; Therapeutic; Therapeutic Intervention; Tissues; Translating; Translational Research; Tumor-Infiltrating Lymphocytes; Vertebrates; Work; base; bench to bedside; career development; design; efficacy testing; experience; genetic analysis; human subject protection; immunogenicity; improved; inhibitor/antagonist; innovation; melanoma; mutant; novel strategies; oncology; pre-clinical; prevent; programs; public health relevance; success

DESCRIPTION 3 OVERALL CRITIQUE 3 SPORE PROGRAM ORGANIZATION AND CAPABILITIES 6 SCIENTIFIC COLLABORATIONS 9 ADDITIONAL REVIEW CRITERIA 10 PROTECTION OF HUMAN SUBJECTS 10 VERTEBRATE ANIMALS 11 BIOHAZARDS 11 FOREIGN ORGANIZATIONS 11 INDIVIDUAL PROJECTS AND CORES 12 PROJECT 1: Potentiating the Effects of Targeted and Cytotoxic Agents on Cell-Based Immunotherapy n Melanoma 12 PROJECT 2: Abrogation of Therapeutic Escape Pathways in BRAF Mutant Melanoma 16 PROJECT 3: Augmenting the Immunogenicity of Melanoma through Manipulation of Histone Deacetylses (HDACs) 22 PROJECT 4: Prospective Study of the Associations between Cutaneous Papillomavirus and Polyomavirus Infections and Squamous Cell Carcinoma 27 CORE A: Tissue, Pathology and Bioinformatics Core 33 CORE B: Biostatistics Core 36 CORE C: Administration and Clinical Trials Core 39 DEVELOPMENTAL RESEARCH PROGRAM 41 CAREER DEVELOPMENT PROGRAM 43 COMMITTEE BUDGET RECOMMENDATIONS 47 SPECIAL EMPHASIS PANEL ROSTER DESCRIPTION (provided by applicant): The long-range goal of the Moffitt Skin SPORE is to promote progress in the prevention and treatment of cutaneous malignancies based on developments in our laboratories that are applied to innovative clinical trials. The bench work in each project is a necessary precursor to carrying out the trials associated with the SPORE, since those investigations will explore new biomarkers and correlative assays that are integral to the translational importance of each trial. The translational endpoints of the trials will provide new data that will lead to further laboratory developments that in turn will iteratively lead to strategies for improved trials. The bench-to-bedside-to-bench interaction is imbedded within the core values of Moffitt as a free-standing cancer center, in which a dedicated group of clinician-investigators with extensive experience in the management of melanoma and non-melanoma skin cancer will work with an outstanding group of basic scientists to accelerate the movement of ideas out of the laboratory to the clinic. The support of the Moffitt Cancer Center and its Comprehensive Melanoma Research Center will be crucial to fulfilling this goal, providing ancillary resources and infrastructure to insure the success of the Moffitt Skin SPORE goals. In this Skin SPORE application, the melanoma projects will focus on research in melanoma biology, immunity and signaling that create opportunities to potentiate current and developing clinical approaches to the treatment of cutaneous malignancies. Project 1 will pave the way for larger randomized phase II or phase III trials of adoptive immunotherapy with tumor infiltrating lymphocytes to support the inclusion of BRAF agents with this promising therapy, based on innovative approaches for how these two modalities should be brought together. Project 2 will support the use of Hsp90 inhibitors to overcome resistance to BRAF inhibition in phase II and III trials, redefining how we look at resistance to targeted therapies. Project 3 represents a paradigm shift that employs epigenetic manipulation to alter how we use immunotherapy, and will justify phase II efficacy testing of the combination of HDAc inhibitors with ipilimumab and other immune stimulants. Project 4 will focus on Human Papilloma Virus (HPV) and Merkel's Cell Polyoma Virus (MCPV) types that could potentially play a key role in the development of non-melanoma skin cancers. We expect that data from Project 4 will justify developing new prevention trials of vaccines for HPV and MCPV to prevent squamous and/or basal cell cancers of the skin. The success of each project and the Moffitt Skin SPORE as a whole will have a major impact on the management of cutaneous malignancies.

描述 3 总体评论 3 孢子囊组织和能力 6 科学合作 9 其他审查标准 10 人类受试者保护 10 脊椎动物 11 生物危害 11 外国组织 11 个人项目和核心 12 项目1： 增强靶向和细胞毒性剂对基于细胞的 黑色素瘤免疫治疗 12 项目二： BRAF突变型黑色素瘤治疗性逃逸途径的消除 16 项目3： 通过操作增强黑色素瘤的免疫原性 组蛋白去乙酰化酶（HDAC） 22 项目4： 皮肤乳头状瘤病毒感染的前瞻性研究 多瘤病毒感染与鳞状细胞癌 27 核心A： 组织、病理学和生物信息学核心 33 核心B： 生物统计学核心 36 核心C： 管理和临床试验核心 39 企业文化 41 职业发展计划 43 委员会的预算建议 47 特别强调小组名册 描述（由申请人提供）：Moffitt皮肤孢子的长期目标是根据我们实验室应用于创新临床试验的发展，促进皮肤恶性肿瘤预防和治疗的进展。每个项目中的实验室工作是开展与SPORE相关试验的必要前提，因为这些研究将探索新的生物标志物和相关测定，这些生物标志物和测定对每个试验的转化重要性不可或缺。试验的转化终点将提供新的数据，这些数据将导致进一步的实验室开发，从而迭代地导致改进试验的策略。Moffitt作为一个独立的癌症中心，其核心价值观中包含了工作台到床边到工作台的互动，其中一组在黑色素瘤和非黑色素瘤皮肤癌管理方面具有丰富经验的专门临床医生-研究人员将与一组优秀的基础科学家合作，加速将想法从实验室转移到临床。莫菲特癌症中心及其综合黑色素瘤研究中心的支持对于实现这一目标至关重要，提供辅助资源和基础设施，以确保莫菲特皮肤孢子目标的成功。在此皮肤孢子应用程序中，黑色素瘤项目将专注于黑色素瘤生物学，免疫和信号传导的研究，为加强目前和发展中的皮肤恶性肿瘤治疗临床方法创造机会。项目1将为采用肿瘤浸润淋巴细胞进行过继免疫治疗的大型随机II期或III期试验铺平道路，以支持将BRAF药物纳入这种有前途的治疗，基于如何将这两种模式结合在一起的创新方法。项目2将支持在II期和III期试验中使用Hsp 90抑制剂克服对BRAF抑制的耐药性，重新定义我们如何看待对靶向治疗的耐药性。项目3代表了一种范式转变，采用表观遗传操作来改变我们使用免疫疗法的方式，并将证明HDAC抑制剂与易普利姆玛和其他免疫刺激剂组合的II期疗效测试是合理的。项目4将重点关注人类乳头瘤病毒（HPV）和默克尔的细胞多瘤病毒（MCPV）类型，这些病毒可能在非黑色素瘤皮肤癌的发展中发挥关键作用。我们预计项目4的数据将证明开发HPV和MCPV疫苗的新预防试验，以预防皮肤鳞状细胞癌和/或基底细胞癌。每个项目的成功和Moffitt皮肤孢子作为一个整体将对皮肤恶性肿瘤的管理产生重大影响。