Clinical Research Support for the CCR

支持癌症研究中心（CCR）的临床服务项目（CSP）实验室如下所示。CCR临床支持实验室（CSL）的专用支持。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还为位于马里兰州Bethesda的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试验支持和发展实验室。该实验室为CCRs分子生物学实验室（Ira Pastan博士，主任）提供专门的支持，以开展以基因工程免疫毒素为重点的研究者发起的研究和临床试验。目前临床正在评估的免疫毒素有3种：1)LMB2治疗某些淋巴瘤，2)BL22治疗成人和儿童某些淋巴瘤和毛细胞白血病，3)HA22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前沿的，临床验证的免疫分析，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，已有7种不同的免疫检测方法被证实可用于临床。LCMI的另一项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，以提供一种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。NCI实验治疗（NExT）项目是癌症治疗与诊断部（DCTD）和癌症研究中心（CCR）之间的合作项目。该项目旨在简化有前景的新型抗癌药物的开发和测试，并加快它们从实验室到临床的交付，充分利用了两个组织的优势。DCTD在药物开发和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项目侧重于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，促进对新的抗癌治疗和显像剂在人体中的快速初步评估。国家临床目标验证实验室（NCTVL）。该国家实验室是应DCTD的要求于2006财年建立的，是DCTD和CCR之间的合作，旨在解决肿瘤药物开发中的机制差距，这种差距往往是由于难以确定治疗干预对患者的假定作用部位的影响而产生的。该实验室是CCR发育治疗临床中心（Developmental Therapeutics Clinic）阐明专门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，证实了在临床前开发期间观察到的小分子抗癌药物对人类感兴趣的特定信号转导途径的治疗效果。国家临床靶标验证实验室的任务是进行验证的分析程序，以测试肿瘤或替代组织的分子靶向治疗的效果。该实验室使用经过验证的靶标分析来评估在CCR治疗的患者中药物对分子靶标的作用，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转移过来。除了为校内CCR研究人员提供支持外，NCTVL还为nci资助的校外研究人员提供患者样本的靶标验证分析，这些校外研究人员缺乏在现场进行此类分析的资源或专业知识。合成化学实验室。合成化学实验室成立于2007年，为dctd发展治疗项目（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，该实验室将重点开展优化活动，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，以指定的先导化合物为基础创建新的类似物，以迭代的方式解决以下问题：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综合方法，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 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.