Clinical Research Support for the CCR

CCR 的临床研究支持

• 批准号: 8350189
• 负责人: Robert Wiltrout
• 金额: $ 189.57万
• 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/8350189
• 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 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; 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; cancer diagnosis; cancer epidemiology; cancer genetics; cancer therapy; 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 the CCR 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 2006 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 NCTVL 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 DCTD's 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.

支持癌症研究中心（CCR）的临床服务计划（CSP）实验室如下所示。 为CCR临床支持实验室（CSL）提供专门支持。CSL为大约33项CCR临床试验提供临床监测、流式细胞术和淋巴因子检测。CSL还在位于马里兰州贝塞斯达的NIH临床中心的实验室空间为CCR临床药理学核心提供临床样本处理和检测支持。 人类癌症免疫毒素治疗检测支持和开发实验室。该实验室为CCR分子生物学实验室（伊拉帕斯坦博士，主任）提供专门支持，以进行以基因工程免疫毒素为重点的免疫启动研究和临床试验。目前，临床上正在评估3种免疫毒素：1）用于某些淋巴瘤的LMB 2，2）用于成人和儿科患者中某些淋巴瘤和毛细胞白血病的BL 22，以及3）HA 22，这是一种正在研究的高亲和力免疫毒素，可替代BL 22。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。该实验室的主要使命是提供尖端的，临床验证的免疫学测定，广泛适用于NCI研究人员，以解决临床和基础研究问题。迄今为止，已验证了7种不同的免疫学测定法用于临床。LCMI的第二个使命是与疫苗工作组监督委员会协调，开发新的免疫学检测方法，为临床环境中细胞介导免疫的不同方面提供更精确和准确的分析方法。支持NCI实验治疗计划NCI实验治疗计划（NExT）是癌症治疗和诊断部门（DCTD）和癌症研究中心（CCR）之间的合作伙伴关系。该计划旨在简化有前途的新抗癌药物的开发和测试，并加快其从实验室到床边的交付，该计划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则以其将基础科学发现转化为临床应用的综合方法而闻名。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的全面开发计划之前，促进对人类新抗癌治疗和成像剂的快速初步评估。国家临床靶点验证实验室（NCTVL）。该国家实验室是应DCTD的要求于2006年建立的，是DCTD和CCR之间的合作，旨在解决肿瘤药物开发中经常出现的机制差距，这是由于确定治疗干预对其患者假定作用部位的影响存在固有困难。该实验室作为一个α位点，用于阐明特别适用于CCR开发治疗诊所的人类癌症早期和I/II期临床试验的新型靶组织方法，证实了小分子抗癌剂对临床前开发期间观察到的人类特定信号转导途径的治疗作用。NCTVL的使命是进行有效的分析程序，以测试肿瘤或替代组织的分子靶向治疗的效果。实验室使用经验证的靶向试验评估药物对CCR内接受治疗的患者分子靶点的影响，其中许多试验将从人体毒理学和药理学实验室（DCTD/SAIC-Frederick，Inc）的药效学试验开发和实施项目中转移。除了为CCR内部研究者提供支持外，NCTVL还为来自NCI资助的外部研究者的患者样本提供靶向验证检测，这些外部研究者缺乏在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开发治疗计划（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，该实验室将集中其活动，以引导优化，新药发现和开发的一个重要组成部分。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，以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。