IND, REGULATORY AND BIOINFORMATICS

IND、监管和生物信息学

• 批准号: 8235931
• 负责人: DARELL D BIGNER
• 金额: $ 15.4万
• 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/8235931
• 关键词: Adjuvant; 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; Epidermal Growth Factor Receptor; 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; Inbreeding; 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; Primary Neoplasm; 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 Antigen; Vaccines; Viral; Xenograft procedure; animal colony; clinical application; design; efficacy evaluation; human monoclonal antibodies; improved; in vivo; mouse model; neuro-oncology; novel; pre-clinical; preclinical efficacy; 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.

参见说明）： 核心A。IND、监管和生物信息学核心。达雷尔湾签名者，医学博士，哲学博士、核心领导 核心A整合了开发、认证、临床前评价、生物统计和监管 将在SRC和单独资助的赠款中进行评估的试剂方面。核心A 提供：1）继续开发和认证针对目标的新试剂， 单独资助的赠款中的基因挖掘方法以及 肽或RNA形式的遗传修饰抗体、免疫毒素和疫苗抗原， 临床应用; 2）准备IND申请并维持所有人的法规合规性 在该SRC或单独资助的赠款中产生的试剂;以及3）协调的信息和统计 中概述的临床前和临床研究设计和实施过程中的监督和分析 SRC和单独资助的赠款。该核心将集中在两个领域：1）嵌合，片段 单克隆抗体的工程、生物化学和基因组生产以及临床前评价， 免疫毒素构建体在无胸腺啮齿动物模型中用于脑内和鞘内隔室治疗， 和2）疫苗策略的体外表征和临床前毒性评价， 结合肽和RNA负载的树突状细胞在免疫活性的小鼠星形细胞瘤中的作用 模型将开发、改进或推进靶向EGFR/EGFRvIII的试剂用于临床试验， GP 240/hmwCSPG、GPNMB、MRP 3和神经节苷脂3 '-isoLM 1和3'，6 '-isoLD 1。必要的 用于产生scFv双抗体、微抗体和CH 2结构域缺失的F（ab '）2 MAb的方法 该核心可改善渗透性、血液清除率和缺乏肾小球截留。大 模拟人CMS疾病的大型和小型动物模型的所有组成部分和可用的施用 路由（例如，（即）用于稳定性、定位能力、免疫学和肿瘤抑制的临床前评价 或开发的药物的杀肿瘤作用也可在本核心中获得。目前我们有多名探员 准备测试和其他几个应该在第一年入学。这种熟悉程度 这些代理商使核心A成为IND准备、统计监督和开发的天然中心， 以及Nautilus和Oracle数据库的应用。 相关性（参见说明）： 该核心提供统计分析，以确保所有实验的正确设计和解释 在这个SRC中。在本核心中进行的实验将确保所有试剂的质量和安全性 临床使用前在本SRC内生产。最后，该核心提供了收集临床 数据和正确的目录，存储和检索有价值的临床标本。