HUMAN IMMUNOLOGIC MONITORING AND CGMP

项目总结（见说明）：免疫疗法在癌症治疗组合中的作用正在迅速增长。最近FDA批准了用于前列腺癌的Provenge疫苗和用于黑色素瘤的抗CTLA-4 mAb ipilimumab，这刺激了对癌症患者新免疫治疗药物的探索。CD 8 * T细胞对肿瘤抗原的特异性识别以及单克隆抗体与肿瘤靶点的结合代表了免疫介导的肿瘤排斥的主要效应机制。这些相互作用的精确特异性使癌症免疫疗法被指定为靶向疗法。最近关于与免疫疗法的临床益处相关的预测性生物标志物的工作正在进一步扩展免疫疗法作为患者特异性疗法的概念。在过去的十年中取得的巨大进展在很大程度上是由于双向翻译研究的成功应用。免疫疗法的合理发展得益于对患者材料的科学终点的仔细分析。人类免疫学筛选-cGMP（HIM-cGMP）设施的主要目的是提供资源，使UCCCC研究人员能够进行新的免疫治疗临床试验。提高现有药物的有效性，开发新的免疫干预措施（如抗癌疫苗），以及阐明研究性治疗的成功与失败的机制，都需要对科学终点进行仔细监测。HIM-cGMP机构是一个专门的实验室，用于评价对影响免疫细胞的药物或干预措施的药效学参数。cGMP Subcore的集成使临床级产品的制备成为可能，例如癌症疫苗，用于患者。该机构还使用淋巴细胞或其他造血细胞作为替代组织监测其他药物（如信号转导抑制剂）的生物学效应。因此，HIM-cGMP设施是UCCCC在癌症免疫治疗方面临床/转化工作的核心，对于其他新型药物的科学研究至关重要。

PROJECT SUMMARY (See instructions): The role of immunotherapy in the portfolio of cancer therapeutics is growing rapidly. The recent FDA approvals of the Provenge vaccine for prostate cancer and the anti-CTLA-4 mAb ipilimumab for melanoma have spurred expanded exploration of new immunotherapeutics in cancer patients. The specific recognition of tumor antigens by CD8* T cells and the binding of monoclonal antibodies to tumor targets represent the main effector mechanisms for immune-mediated tumor rejection. The exquisite specificity of these interactions has earned cancer immunotherapy the designation as a targeted therapy. Recent work on predictive biomarkers associated with clinical benefit from immunotherapies is expanding the notion of immunotherapy further as a patient-specific therapy. The tremendous progress made over the past decade is to a large extent due to the successful application of bidirectional translational research. Rational development of immunotherapies has benefitted from careful analysis of scientific endpoints from patient material. The main purpose of the Human Immunologic Monitoring-cGMP (HIM-cGMP) Facility is to provide the resources to enable UCCCC investigators to conduct novel immunotherapy clinical trials. Improving upon the effectiveness of current agents, developing new immunotherapeutic interventions (such as anti-cancer vaccines), and elucidating the mechanism of success versus failure of investigational treatments, all require careful monitoring of scientific endpoints. The HIM-cGMP Facility serves as a specialized laboratory for evaluating pharmacodynamic parameters in response to agents or interventions that impact on immune cells. The integration of the cGMP Subcore enables the preparation of clinical grade products, such as cancer vaccines, for administration to patients. The Facility also monitors biologic effects of other pharmacologic agents (such as signal transduction inhibitors) using lymphocytes or other hematopoiefic cells as a surrogate tissue. The HIM-cGMP Facility therefore lies at the heart of the UCCCC's clinical/translational effort in cancer immunotherapy, and is vital for the scientific investigation of additional novel agents.