IND, REGULATORY AND BIOINFORMATICS

IND、监管和生物信息学

• 批准号: 8106241
• 负责人: DARELL D BIGNER
• 金额: $ 16.57万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8106241
• 关键词: Animal Model; Animals; Antibodies; Area; Astrocytoma; Autologous; Biochemical; Bioinformatics; Biological Assay; Biological Models; Blood; Cataloging; Catalogs; Certification; Clinical; Clinical Data; Clinical Research; Clinical Trials; Communities; Complex; Conjugate Vaccines; Contracts; Data; Data Analyses; Data Base Management; Databases; Dendritic Cells; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Documentation; Drug Compounding; Engineering; Ensure; Evaluation; Familiarity; Fostering; Funding; Gangliosides; Generations; Genes; Genomics; Glioma; Grant; Health Insurance Portability and Accountability Act; Human; Human Biology; Immunocompetent; Immunoglobulin Fragments; Immunologics; Immunotoxins; In Vitro; Informatics; Investigational Drugs; Investigational New Drug Application; Knowledge; Label; Laboratories; Maintenance; Maximum Tolerated Dose; Methodology; Mining; Modeling; Monoclonal Antibodies; Mus; Nautilus; Penetration; Peptides; Performance; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Positioning Attribute; Preparation; Production; Pyrogens; Quality Control; RNA; Radioisotopes; Rattus; Reagent; Regulation; Research; Research Infrastructure; Resource Informatics; Resources; Rodent; Rodent Model; Role; Route; Safety; Source; Specimen; Sterility; System; Testing; Therapeutic; Therapeutic Agents; Toxic effect; Toxicity Tests; Translations; Vaccine Adjuvant; Vaccine Antigen; Vaccines; Viral; Xenograft procedure; animal colony; clinical application; design; efficacy evaluation; glycoprotein NMB; improved; in vivo; mouse model; neuro-oncology; novel; pre-clinical; preclinical evaluation; preclinical toxicity; programs; research clinical testing; research study; safety testing; subcutaneous; tumor; tumor xenograft; vaccine evaluation

Seeinstructions): Core A. IND, Regulatory, and Bioinformatics Core. Darell D. Signer, M.D., Ph.D., Core Leader Core A integrates the development, certification, pre-clinical evaluation, biostatistical and regulatory aspects of reagents that will be evaluated in the SRC and separately funded grants. Specifically, Core A provides: 1) continued development and certification of new reagents directed against targets identified by gene mining approaches in separately funded grants and the establishment and characterization of genetically modified antibodies, immunotoxins, and vaccine antigens in the form of peptides or RNA for clinical application; 2) preparation of IND applications and maintenance of regulatory compliance for all reagents generated in this SRC or in separately funded grants; and 3) coordinated informatic and statistical oversight and analysis during the design and conduct of the pre-clinical and clinical studies outlined in the SRC and in separately funded grants. This Core will focus on two areas: 1) chimerization, fragment engineering, biochemical and genomic production and pre-clinical evaluation of monoclonal antibody and immunotoxin constructs in athymic rodent models for intracerebal and intrathecal compartmental therapy, and 2) in vitro characterization and pre-clinical toxicity evaluation of vaccine strategies consisting of conjugated peptides and RNA-loaded dendritic cells in immunocompetent syngeic murine astrocytoma models. Reagents will be developed, refined, or advanced to clinical trial that target EGFR/EGFRvlll, GP240/hmwCSPG, GPNMB, MRP3, and gangliosides 3'-isoLM1 and 3',6'-isoLD1. The requisite methodology for the generation of scFv diabodies, minibodies, and CH2 domain-deleted F(ab')2 MAbs for improved penetration, blood clearance, and lack of glomerular trapping is available in this Core. A large repertoire of large and small animal models that mimic human CMS disease and available administration routes (e.g. i.t. and i.e.) for preclinical evaluation of stability, localizing ability, immunologic, and tumoristatic or tumoricidal effect of developed agents is also available in this Core. We have multiple agents currently ready for testing and several others that should matriculate during the first year. This level of familiarity with these agents makes Core A a natural hub for IND preparation, statistical oversight, and the development and application of Nautilus and Oracle databases as well. RELEVANCE (Seeinstructions): This Core provides the statistical analysis to ensure proper design and interpretation of all experiments performed in this SRC. Experiments performed in this Core will ensure the quality and safety of all reagents produced within this SRC before clinical use. Finally, this Core provides the infrastructure to collect clinical data and to properly catalog, store and retrieve valuable clinical specimens.

请参阅说明)： 核心A.IND、监管和生物信息学核心。Darell D.Siger，医学博士，核心领导者 核心A集开发、认证、临床前评估、生物统计和监管为一体 试剂的方面，将在SRC和单独资助的赠款中进行评估。具体地说，核心A 提供：1)针对下列确定的目标继续开发和认证新试剂 单独资助赠款中的基因挖掘方法以及建立和表征 以多肽或RNA形式的转基因抗体、免疫毒素和疫苗抗原 临床应用；2)准备IND申请并维护所有人遵守法规 在本SRC或单独资助的赠款中产生的试剂；以及3)协调信息和统计 在设计和进行临床前和临床研究期间的监督和分析 SRC和单独资助的赠款。这个核心将集中在两个领域：1)嵌合化，片段 单抗的工程、生化和基因组生产及临床前评价 用于脑内和鞘内隔室治疗的无性系啮齿动物模型中的免疫毒素结构， 和2)疫苗策略的体外特征和临床前毒性评估，包括 免疫活性合并型小鼠星形细胞瘤中的结合肽和RNA负载树突状细胞 模特们。针对EGFR/EGFRv11的试剂将被开发、改进或推进到临床试验， GP240/hmwCSPG、GPNMB、MRP3和神经节苷脂3‘-isLM1和3’，6‘-isLD1。必备条件 单链抗体、微抗体和CH2结构域缺失的F(ab‘)2单抗的制备方法 这种核心可以改善穿透性、血液清除性和减少肾小球陷阱。大号 模拟人类CMS疾病的大小动物模型和可用药物 路线(例如，I.T.以及，即)用于稳定性、定位能力、免疫学和肿瘤稳定性的临床前评估 或者开发的药物的杀瘤作用也可以在这个核心中获得。我们目前有多个代理 准备考试，以及其他几个应该在第一年录取的学生。对这种程度的熟悉 这些代理使Core A成为IND准备、统计监督和开发的天然枢纽 以及Nautilus和Oracle数据库的应用。 相关性(请参阅说明)： 此核心提供统计分析，以确保所有实验的正确设计和解释 在此SRC中执行。在该核心进行的实验将确保所有试剂的质量和安全 在临床使用前在本SRC内生产。最后，这个核心提供了收集临床数据的基础设施 数据，并适当编目、存储和检索有价值的临床标本。