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.

下面突出显示了支持癌症研究中心（CCR）的临床服务计划（CSP）实验室。 对CCR临床支持实验室（CSL）的专用支持。 CSL提供了大约33次CCR临床试验，提供临床监测，流式细胞仪和淋巴因子测试。 CSL还为位于马里兰州贝塞斯达NIH临床中心的实验室空间的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法支持和开发实验室。该实验室为研究人员发起的研究和临床试验的CCR分子生物学实验室（IRA Pastan博士）提供了专门的支持，重点是基因设计的免疫毒素。目前，临床评估了3种免疫毒素：1）某些淋巴瘤的LMB2，2）对于成人和儿科患者的某些淋巴瘤和毛状细胞白血病的2）BL22，以及3）HA22，这是研究中的高亲和力免疫毒素，可取代BL22。细胞介导的免疫（LCMI）实验室。 LCMI提供了专门的支持，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最先进的，临床上验证的免疫学测定，这些测定法广泛适用于NCI研究人员，以解决临床和基础研究问题。迄今为止，已经对7种不同的免疫学测定进行了验证，以供临床使用。 LCMI的次要任务是与疫苗工作组监督委员会协调开发，这是新的免疫学测定，可以提供更精确，更准确的方法来分析临床环境中细胞介导的免疫的不同方面。对NCI实验治疗计划的支持NCI实验治疗方法（下一个）计划是癌症治疗和诊断分区（DCTD）与癌症研究中心（CCR）之间的伙伴关系。旨在简化有希望的新抗癌药物的开发和测试，并加快从板凳上的床边交付，该计划利用了两个组织的优势。 DCTD在药物开发和与制药和生物技术公司的关系方面具有长期的专业知识，而CCR以其全面的方法将基础科学发现转化为临床应用而闻名。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。下一个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促进人类中新的抗癌治疗和成像剂的快速初步评估，然后再将时间和资源用于大规模，完整的发展计划。国家临床目标验证实验室（NCTVL）。该国家实验室于2006年应DCTD的要求成立，是DCTD和CCR之间的合作，旨在解决肿瘤药物开发中经常发生的机械差距，这是由于确定治疗性干预对患者推定的采取效应部位的影响而经常发生的。该实验室是阐明在CCR发育疗法诊所中专门适用于人类癌症早期和I/II期临床试验的新型目标组织方法论的α位点，证实了小分子抗癌药对人类感兴趣的特定信号转移途径的小分子抗癌药对人类感兴趣的特定信号传输途径的治疗作用，这些疗程是在预防范围内观察到的。 NCTVL的任务是进行经过验证的测定程序，以测试肿瘤或替代组织，以实现分子靶向疗法的作用。该实验室使用经过验证的靶标测定法评估了在CCR治疗的患者中对分子靶标的药物影响，其中许多将从人类毒理学和药理学实验室（DCTD/SAIC-Frederick，Inc）的药效学分析开发和实施计划中转移。除了为CCR内研究人员提供支持外，NCTVL还为来自NCI资助的校外调查人员的患者样本提供了目标验证测定，缺乏资源或专业知识来进行现场进行此类测定。合成化学实验室。合成化学实验室成立于2007年，目的是为DCTD发育疗法计划（DTP）的药物发现和开发工作提供化学支持，并由DCTD-CCR联合发展委员会批准的项目。为此，实验室将集中精力进行优化，这是新药发现和开发的重要组成部分。将开发出新的合成方法，以基于指定的铅化合物来创建新的类似物，以通过迭代方式解决以下方式：活动，选择性，亲脂性，生物利用度，稳定性和ADME/PK。该实验室将为更广泛的NCI壁外社区的应用开发新的相关综合方法。