HUMAN IMMUNOLOGIC MONITORING AND CGMP

项目概述（见说明书）：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单抗ipilimumab，这刺激了对癌症患者新免疫疗法的进一步探索。CD8* T细胞对肿瘤抗原的特异性识别和单克隆抗体与肿瘤靶点的结合是免疫介导的肿瘤排斥反应的主要效应机制。这些相互作用的精细特异性为癌症免疫疗法赢得了靶向治疗的称号。最近对与免疫治疗临床获益相关的预测性生物标志物的研究，正在进一步扩大免疫治疗作为患者特异性治疗的概念。过去十年的巨大进步在很大程度上归功于双向转化研究的成功应用。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。人类免疫监测- 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，开发新的免疫治疗干预措施（如抗癌疫苗），阐明研究性治疗成功与失败的机制，都需要仔细监测科学终点。HIM-cGMP设施是一个专门的实验室，用于评估影响免疫细胞的药物或干预措施的药效学参数。cGMP Subcore的整合可以制备临床级产品，如癌症疫苗，供患者使用。该设施还监测使用淋巴细胞或其他造血细胞作为替代组织的其他药物制剂（如信号转导抑制剂）的生物效应。因此，HIM-cGMP设施是UCCCC癌症免疫治疗临床/转化工作的核心，对其他新药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.