HUMAN IMMUNOLOGIC MONITORING AND CGMP

人体免疫监测和 CGMP

• 批准号: 8486629
• 负责人: MICHELLE M LE BEAU
• 金额: $ 12.77万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486629
• 关键词: Binding; Biological Markers; Biological Monitoring; CD8B1 gene; Cancer Center Support Grant; Cancer Patient; Cancer Vaccines; Cells; Clinical; Clinical Trials; Core Facility; Cyclic GMP; Development; Effectiveness; Environment; Failure; Funding; Heart; Hematopoietic; Human; Immune; Immune response; Immunologic Monitoring; Immunologics; Immunotherapeutic agent; Immunotherapy; Instruction; Intervention; Investigation; Investigational Therapies; Joints; Laboratories; Lymphocyte; Malignant Neoplasms; Measures; Mediating; Monitor; Monoclonal Antibodies; Outcome; Patients; Pharmacodynamics; Phase; Philanthropic Fund; Preparation; Production; Prostate Cancer Vaccine; Research Personnel; Resources; Role; Services; Signal Transduction Inhibitor; Specificity; Study Subject; T-Lymphocyte; Therapeutic; Time; Tissues; Translational Research; Tumor Antigens; Work; cancer immunotherapy; design; improved; melanoma; novel; response; success; translational clinical trial; tumor

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.

项目摘要（参见说明）：免疫疗法在癌症治疗组合中的作用正在迅速增长。最近 FDA 批准了治疗前列腺癌的 Provenge 疫苗和治疗黑色素瘤的抗 CTLA-4 单克隆抗体 ipilimumab，这刺激了癌症患者新免疫疗法的探索。 CD8* 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标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赢得了靶向疗法的称号。最近对与免疫疗法临床获益相关的预测生物标志物的研究正在进一步扩展免疫疗法作为患者特异性疗法的概念。过去十年取得的巨大进步很大程度上得益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 研究人员能够开展新型免疫治疗临床试验。提高现有药物的有效性、开发新的免疫治疗干预措施（例如抗癌疫苗）以及阐明研究性治疗成功与失败的机制，所有这些都需要仔细监测科学终点。 HIM-cGMP 设施作为一个专业实验室，用于评估药效学参数，以响应影响免疫细胞的药物或干预措施。 cGMP 子核心的集成使得能够制备临床级产品，例如用于给患者施用的癌症疫苗。该设施还使用淋巴细胞或其他造血细胞作为替代组织来监测其他药物（例如信号转导抑制剂）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，对于其他新型药物的科学研究至关重要。