Clinical Research Support for the CCR

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CCR临床试验提供临床监测、流式细胞仪和淋巴因子检测。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测试支持。人类癌症免疫毒素治疗分析支持和发展实验室。该实验室为CCR分子生物学实验室(首席执行官Ira Pastan博士)提供专门的支持，用于研究人员发起的研究和侧重于基因工程免疫毒素的临床试验。目前，3种免疫毒素正在进行临床评估：1)LMB2用于某些淋巴瘤，2)BL22用于某些淋巴瘤和成人和儿童患者的毛细胞白血病，以及3)HA22，这是一种正在研究中的高亲和力免疫毒素，以取代BL22。细胞免疫实验室(LCMI)。LCMI提供专门的支持，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尖端的、经临床验证的免疫分析方法，这些方法广泛适用于NCI研究人员，以解决临床和基础研究问题。到目前为止，已有7种不同的免疫学检测方法被证实可用于临床。LCMI的次要任务是与疫苗工作组监督委员会协调开发新的免疫分析方法，以提供更精确和准确的手段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(NEXT)计划是癌症治疗和诊断部(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景的抗癌新药的开发和测试，并加快它们从试验台到床边的交付，该计划利用了这两个组织的优势。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全面方法而闻名世界。该计划还旨在为NCI的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的作用。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，促进对新的抗癌治疗和成像药物在人体上的快速初步评估。国家临床目标验证实验室(NCTVL)。这个国家实验室是应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，这是因为在确定治疗干预对患者推定作用部位的效果方面存在固有困难。该实验室作为一个阿尔法场所，在CCR开发治疗诊所阐明专门适用于人类癌症早期阶段和I/II期临床试验的新的靶向组织方法，确认小分子抗癌剂对临床前开发期间观察到的人类感兴趣的特定信号转导途径的治疗效果。NCTVL的任务是进行经过验证的分析程序，以测试肿瘤或替代组织分子靶向治疗的效果。该实验室使用有效的靶标分析来评估在CCR内治疗的患者的药物对分子靶标的影响，其中许多将从人类毒理学和药理学实验室(DCTD/SAIC-Frederick，Inc.)的药效分析开发和实施计划中转移过来。除了为CCR内部调查人员提供支持外，NCTVL还为NCI资助的缺乏现场进行此类分析的资源或专业知识的外部调查人员的患者样本提供目标验证分析。合成化学实验室。合成化学实验室成立于2007年，旨在为DCTD的开发治疗计划(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，该实验室将其活动重点放在铅的优化上，这是新药发现和开发的一个基本和不可或缺的部分。正在开发新的合成方法，以基于所分配的先导化合物来创建新的类似物，以通过迭代的方式解决以下问题来改善药物概况：活性、选择性、亲脂性、生物利用度、稳定性和ADME/PK。该实验室正在开发新的相关合成方法，供更广泛的NCI校外社区应用。

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 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 focuses its activities on lead optimization, an essential and integral part of new drug discovery and development. Novel synthetic methodologies are being 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 is developing new relevant synthesis methodologies for applications by the wider NCI extramural community.