Core-006

摘要 人类免疫监测和当前良好生产规范(HIMcGMP)机制的主要目的是为芝加哥大学医学综合研究所的研究人员提供支持 癌症中心(UCCCC)通过准备疫苗和其他方式进行免疫治疗临床试验 用于患者管理的新免疫疗法，并通过评估来自 病人样本。信息系统分核心于1999年启动，是一个发展中的核心，并一直在 导演托马斯·加杰斯基，医学博士，自那时起。2002年，HIM核心设施成为一个完整的CCSG 核心。CGMP亚核于2001年作为UCCCC开发核心启动，并一直在 由Amittha Wickrema博士指导，自成立以来。2011年，信息系统设施正式与 CGMP设施，简化了两个组成部分之间的接口，包括共享的技术人员。 随着免疫治疗在肿瘤治疗中的作用越来越大，HIMcGMP设施的活动对新型AGEs的科学研究至关重要，并正在迅速扩大。在……里面 除了提供标准的检测方法来测量免疫终点和监测生物效应外 其他使用淋巴细胞作为替代组织的药物，这种可能性已经整合了新的 促进患者新生物标记物研究的技术。例如，UCCCC调查人员首先 描述了T细胞炎症/非炎症肿瘤微环境基因表达谱 探索作为检查点阻断治疗反应的预测生物标志物。了解 这种自发的抗肿瘤T细胞反应在一些患者中发展的机制，以及 在其余患者中发生免疫排斥的机制是强调 耐药性和新的治疗靶点。HIM-cGMP设施整合了新技术， 促进识别这些机制。该设施最近购买了一个纳米串计数器 能够对福尔马林固定石蜡包埋(FFPE)组织进行基因表达谱分析的仪器，如 以及RNAScope系统，用于可视化特定mRNAs的原位表达。此外，新的协议 用于微生物区系测序的银行粪便，用于种系DNA分析的血液，以及用于专门化的血清 生化分析已经发展起来。因此，除了标准的免疫学分析外，HIM-cGMP 该设备有助于分析肿瘤中突变模式之间的多维相关性， 胚系遗传多态和肠道微生物区系的组成，所有这些都与 免疫治疗的临床结果。

ABSTRACT The main purpose of the Human Immunologic Monitoring and Current Good Manufacturing Practice (HIMcGMP) Facility is to provide support to investigators at the University of Chicago Medicine Comprehensive Cancer Center (UCCCC) who conduct immunotherapy clinical trials through preparing vaccines and other novel immunotherapies for patient administration, and by evaluating various immunologic endpoints from patient samples. The HIM Subcore was initiated in 1999 as a Developing Core and has been under continuous direction by Thomas Gajewski, MD, PhD, since that time. In 2002, the HIM Core Facility became a full CCSG Core. The cGMP Subcore was initiated as a UCCCC Developing Core in 2001 and has been under continuous direction by Amittha Wickrema, PhD, since its inception. In 2011, the HIM Facility formally merged with the cGMP Facility, which streamlined the interface between the two components, including shared technical staff. With the increasing role of immunotherapy in the portfolio of cancer therapeutics, the activities of the HIMcGMP Facilty are vital for the scientific investigation of novel agen and have been expanding rapidly. In addition to providing standard assays to measure immunologic endpoints and to monitor biologic effects of other pharmacologic agents using lymphocytes as a surrogate tissue, the Facilty has integrated new technologies to facilitate the study of novel biomarkers in patients. For example, UCCCC investigators first described the T cell-inflamed/non-inflamed tumor microenvironment gene expression profile that has been explored as a predictive biomarker for response to checkpoint blockade therapy. Understanding the mechanism by which this spontaneous anti-tumor T cell response develops in some patients, and the mechanism by which immune exclusion occurs in the remaining patients, is highlighting mechanisms of resistance and new therapeutic targets. The HIM-cGMP Facility has integrated new technologies that are facilitating identification of these mechanisms. The Facility recently purchased a Nanostring nCounter instrument, which enables gene expression profiling from formalin-fixed paraffin-embedded (FFPE) tissue, as well as an RNAscope system, for visualizing in situ expression of specific mRNAs. In addition, new protocols for banking stool for microbiota sequencing, blood for germline DNA analysis, and serum for specialized biochemical assays have been developed. Thus, in addition to standard immunologic assays, the HIM-cGMP Facility is facilitating the analysis of multidimensional correlations between mutational patterns in the tumor, germline genetic polymorphisms, and the composition of intestinal micriobiota, all with respect to immunotherapy clinical outcome.