Clinical Research Support for the CCR

CCR 的临床研究支持

• 批准号: 7970207
• 负责人: Robert Wiltrout
• 金额: $ 157.61万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/7970207
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adult; Affinity; Antineoplastic Agents; Antiviral Agents; Autoimmunity; BL22 immunotoxin; Basic Science; Biological; Biological Assay; Biological Availability; Biotechnology; Cellular Immunity; Chemistry; Childhood; Chronic Granulomatous Disease; Clinic; Clinical; Clinical Pharmacology; Clinical Research; Clinical Services; Clinical Trials; Collaborations; Commit; Communities; Cryopreservation; Development; Developmental Therapeutics Program; Disease; Division of Cancer Epidemiology and Genetics; Division of Cancer Treatment and Diagnosis; Drug effect disorder; Drug resistance; Engineering; Evaluation; Extramural Activities; Flow Cytometry; Functional disorder; Funding; Generations; Goals; Hairy Cell Leukemia; Human; Image; Immune; Immunologics; Immunotoxin Therapy; Immunotoxins; Industry; Joints; Laboratories; Laboratory Research; Lead; Lymphokines; Lymphoma; Malignant Neoplasms; Maryland; Methodology; Mission; Molecular Biology; Molecular Target; Monitor; Mutation; NCI Center for Cancer Research; National Institute of Allergy and Infectious Disease; Patient Monitoring; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacology and Toxicology; Phase; Procedures; Process; Research Personnel; Research Support; Resistance development; Resources; Sampling; Scientist; Signal Transduction Pathway; Site; Synthesis Chemistry; Testing; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Time; Tissues; Translating; United States National Institutes of Health; Vaccination; Vaccines; Validation; Viral; Viral Load result; analog; anti-cancer therapeutic; anticancer research; assay development; base; bench to bedside; clinical application; clinical material; design; drug development; drug discovery; immune function; improved; interest; lipophilicity; meetings; novel; pre-clinical; programs; response; small molecule; tumor; working group

Clinical Services Program (CSP) laboratories that support the Center for Cancer Research (CCR) are highlighted below. Dedicated Support for the CCR Clinical Support Laboratory (CSL). The CSL provides clinical monitoring, flow cytometry, and lymphokine testing for approximately 33 CCR clinical trials. The CSL also provides clinical sample processing and testing support to the CCR Clinical Pharmacology Core in lab space located at the NIH Clinical Center in Bethesda, Maryland. Human Cancer Immunotoxin Therapy Assay Support and Development Laboratory. This laboratory provides dedicated support to CCRs Laboratory of Molecular Biology (Dr. Ira Pastan, Chief), for investigator-initiated studies and clinical trials focusing on genetically engineered immunotoxins. Currently, 3 immunotoxins are being evaluated clinically: 1) LMB2 for certain lymphomas, 2) BL22 for certain lymphomas and hairy cell leukemia in adult and pediatric patients, and 3) HA22, which is a high-affinity immunotoxin under study to replace BL22. Laboratory of Cell-Mediated Immunity (LCMI). The LCMI provides dedicated support to meet the requirements of the NCI Vaccine Working Group Oversight Committee. The primary mission of this laboratory is to provide cutting-edge, clinically validated immunological assays that are broadly applicable to NCI investigators to address both clinical and basic research questions. To date, 7 different immunological assays have been validated for clinical use. A secondary mission of the LCMI is to develop, in coordination with the Vaccine Working Group Oversight Committee, new immunological assays that can provide a more precise and accurate means of analyzing different aspects of cell-mediated immunity in clinical settings. Support for the NCI Experimental Therapeutics Program The NCI Experimental Therapeutics (NExT) Program is a partnership between the Division of Cancer Treatment and Diagnosis (DCTD) and the Center for Cancer Research (CCR). Aimed at streamlining the development and testing of promising new anticancer drugs and expediting their delivery from the bench to the bedside, the program capitalizes on the strengths of both organizations. The DCTD has longstanding expertise in drug development and relationships with pharmaceutical and biotechnology companies, while the CCR is world renowned for its comprehensive approach to translating basic science discoveries into clinical applications. The program is also designed to provide opportunities for NCI researchers to collaborate with external academic and industry scientists. The NExT Program focuses on assessing drug action early in the drug-development process. The fundamental goal of these early-phase trials is to facilitate fast initial evaluation of new anticancer therapeutic and imaging agents in humans before committing time and resources to a large-scale, full developmental plan. National Clinical Target Validation Laboratory (NCTVL). This national laboratory was established in FY06 at the request of the DCTD and is a collaboration between the DCTD and CCR aimed at addressing the mechanistic gap in oncologic drug development that frequently occurs due to the difficulties inherent in determining the effect of a therapeutic intervention on its putative site of action in patients. The laboratory serves as an alpha site for the elucidation of novel target tissue methodologies specifically applicable to human cancer early-phase and Phase I/II clinical trials in the CCR Developmental Therapeutics Clinic, confirming the therapeutic effects of small molecule anticancer agents on specific signal transduction pathways of interest in humans that were observed during preclinical development. The mission of the National Clinical Target Validation Laboratory is to conduct validated assay procedures to test tumor or surrogate tissues for effects of molecularly targeted therapies. The laboratory assesses drug effects on molecular targets in patients treated within CCR using validated target assays, many of which will be transferred from the pharmacodynamic assay development and implementation program of the Laboratory of Human Toxicology and Pharmacology (DCTD/SAIC-Frederick, Inc). In addition to providing support for CCR intramural investigators, the NCTVL also provides target validation assays for patient samples from NCI-funded extramural investigators lacking the resources or expertise to conduct such assays on site. Laboratory of Synthetic Chemistry. The Laboratory of Synthetic Chemistry was established in 2007 to provide chemistry support to the drug discovery and development efforts of the DCTDs Developmental Therapeutics Program (DTP) and the projects approved by the Joint Development Committee of DCTD-CCR. Towards this end, the laboratory will focus its activities to lead optimization, an essential and integral part of new drug discovery and development. Novel synthetic methodologies will be developed to create new analogs based on the assigned lead compounds to improve pharmaceutical profiles by addressing the following in an iterative manner: activity, selectivity, lipophilicity, bioavailability, stability, and ADME/PK. The lab will develop new relevant synthesis methodologies for applications by the wider NCI extramural community.

下面重点介绍了支持癌症研究中心 (CCR) 的临床服务计划 (CSP) 实验室。为 CCR 临床支持实验室 (CSL) 提供专门支持。 CSL 为大约 33 个 CCR 临床试验提供临床监测、流式细胞术和淋巴因子检测。 CSL 还为位于马里兰州贝塞斯达 NIH 临床中心实验室空间的 CCR 临床药理学核心提供临床样品处理和测试支持。人类癌症免疫毒素治疗测定支持和开发实验室。该实验室为 CCR 分子生物学实验室（主任 Ira Pastan 博士）提供专门支持，以支持研究者发起的针对基因工程免疫毒素的研究和临床试验。目前，临床上正在评估3种免疫毒素：1）LMB2用于某些淋巴瘤，2）BL22用于成人和儿童患者的某些淋巴瘤和毛细胞白血病，3）HA22，这是一种正在研究替代BL22的高亲和力免疫毒素。细胞介导免疫实验室（LCMI）。 LCMI 提供专门支持，以满足 NCI 疫苗工作组监督委员会的要求。该实验室的主要任务是提供尖端的、经过临床验证的免疫学检测方法，广泛适用于 NCI 研究人员解决临床和基础研究问题。迄今为止，已有 7 种不同的免疫学检测方法经过验证可用于临床。 LCMI 的第二个任务是与疫苗工作组监督委员会协调开发新的免疫学测定方法，以提供更精确和准确的方法来分析临床环境中细胞介导免疫的不同方面。 对 NCI 实验治疗计划的支持 NCI 实验治疗 (NExT) 计划是癌症治疗和诊断部门 (DCTD) 与癌症研究中心 (CCR) 之间的合作伙伴关系。该计划旨在简化有前景的新型抗癌药物的开发和测试，并加快其从实验室到临床的交付，充分利用了两个组织的优势。 DCTD 在药物开发以及与制药和生物技术公司的关系方面拥有长期的专业知识，而 CCR 以其将基础科学发现转化为临床应用的综合方法而闻名于世。该计划还旨在为 NCI 研究人员提供与外部学术和行业科学家合作的机会。 NExT 计划的重点是在药物开发过程的早期评估药物作用。这些早期试验的基本目标是在投入时间和资源进行大规模、全面的开发计划之前，促进新的抗癌治疗和成像剂在人体中的快速初步评估。国家临床靶标验证实验室（NCTVL）。该国家实验室是应 DCTD 的要求于 2006 财年成立的，是 DCTD 和 CCR 之间的合作项目，旨在解决肿瘤药物开发中的机制差距，这种差距经常由于确定治疗干预对其假定的患者作用部位的影响而存在固有的困难而出现。该实验室是 CCR 发展治疗诊所阐明特别适用于人类癌症早期和 I/II 期临床试验的新型靶组织方法的 alpha 站点，证实了小分子抗癌药物对临床前开发过程中观察到的人类感兴趣的特定信号转导途径的治疗作用。国家临床靶标验证实验室的使命是进行经过验证的检测程序，以测试肿瘤或替代组织的分子靶向治疗效果。该实验室使用经过验证的靶点测定来评估药物对 CCR 治疗患者的分子靶点的影响，其中许多测定将从人类毒理学和药理学实验室 (DCTD/SAIC-Frederick, Inc) 的药效测定开发和实施计划中转移。除了为 CCR 校内研究人员提供支持外，NCTVL 还为 NCI 资助的校外研究人员提供的患者样本进行目标验证检测，而这些研究人员缺乏现场进行此类检测的资源或专业知识。 合成化学实验室。合成化学实验室成立于2007年，为DCTD发展治疗计划（DTP）的药物发现和开发工作以及DCTD-CCR联合开发委员会批准的项目提供化学支持。为此，该实验室将把其活动重点放在领先优化上，这是新药发现和开发的重要组成部分。将开发新的合成方法，以基于指定的先导化合物创建新的类似物，通过以迭代方式解决以下问题来改善药物特性：活性、选择性、亲脂性、生物利用度、稳定性和 ADME/PK。该实验室将开发新的相关合成方法，供更广泛的 NCI 校外社区应用。