MD Anderson Cancer Immune Monitoring and Analysis Center MDA-CIMAC

摘要 免疫疗法(Imt)已经成为一种很有前途的治疗策略，适用于广泛的人类 在多种药物，特别是免疫检查点抑制剂的作用下，癌症在各种疾病中显示出令人振奋的结果 癌症的类型。它的全部潜力尚未实现，部分原因是缺乏预测反应的生物标记物。 去接受治疗。基于治疗前分析的多个免疫和基因组生物标志物的反应 已经描述了样本，但大多数都不是很健壮，响应者和 无回应者。因此，有一个关键的未得到满足的需求，以执行全面的特征 在早期IMT试验中使用标准化分析和新方法的候选生物标记物。认识 需要进行全面的免疫监测进行IMT临床试验，NCI在2017年开发了癌症免疫 监测和分析中心(CIMAC)和癌症免疫数据共享中心(CIDC)网络，与 识别应答、耐药和不良事件的生物标记物以优化免疫治疗的目标 癌症患者的治疗方法。MD安德森癌症免疫监测与分析中心 (MDA-CIMAC)是五年前建立的四个CIMAC网站之一，该网站一直在标准化基因组， 接受治疗的患者的组织和血液样本的病理和免疫学分析及辅助分析 在IMT试验中。MDA-CIMAC将由著名的癌症外科和分子医生Ignacio Wistuba博士共同领导 病理学家，Gheath Al-Atrash，著名的内科肿瘤学家，在干细胞移植和 免疫疗法和Cara Hayaker，在免疫生物标记物分析方面的专业知识的癌症免疫学家。他们 将由世界级和高度协作的癌症和癌症专家组成的多学科团队提供支持 免疫疗法。MDA-CIMAC的主要目标是：1)提供一个集中协调的平台 样本收集、处理和质量保证，以及2)使用经过分析验证和标准化的(Tiers 1和2)和高度创新的(Tier 3)分析，可提供表型、基因组和功能分析 参加IMT临床试验的患者的反应特征。在目标1中，我们将使用标准 遵循开发的CIMAC伞形协议的操作程序(SOP)，以提供以下服务 NCI发起的早期免疫治疗中注释生物检疫菌的加工和分布 临床试验并将样本与相关的临床、病理、免疫和分子数据联系起来 CIMAC-CIDC网络。在目标2中，我们将进行常规和创新的病理学、免疫学和 使用标准化、经验证和高度创新的分析方法进行分子分析，以帮助完成NCI- 赞助早期临床试验和开发新的预测IMT生物标记物。在目标3中，在 我们将与CIDC团队合作，为数据收集和计算提供生物统计和计算服务 分析，并将执行、解释和预测高维(组)数据的建模。我们设想， 随着我们在癌症免疫治疗方法方面取得有意义的进展，MDA-CIMAC将是不可或缺的。

ABSTRACT Immunotherapy (IMT) has emerged as a promising treatment strategy across a broad spectrum of human cancers, with multiple agents, particularly immune check point inhibitors, showing promising results in various types of cancers. Its full potential has yet to be realized, due in part, to a lack of biomarkers predicting response to treatment. Multiple immune and genomic biomarkers of response based on analysis of pre-treatment specimens have been described but most are not very robust with significant overlap between responders and non-responders. Therefore, there is a critical unmet need to perform comprehensive characterization of candidate biomarkers in early phase IMT trials using standardized assays and novel methodologies. Recognizing the need for comprehensive immune monitoring for IMT clinical trials, in 2017 NCI developed the Cancer Immune Monitoring and Analysis Center (CIMAC) and Cancer Immunologic Data Commons (CIDC) Network, with the goal of identifying biomarkers of response, resistance, and adverse events to optimize immunotherapy approaches for patients with cancer. The MD Anderson Cancer Immune Monitoring and Analysis Center (MDA-CIMAC) is one of four CIMAC sites established five years ago that has been standardizing genomic, pathology and immunology assays and supporting profiling of tissue and blood specimens from patients treated in IMT trials. The MDA-CIMAC will be co-led by Drs. Ignacio Wistuba, renowned cancer surgical and molecular pathologist, Gheath Al-Atrash, well-known medical oncologist with expertise in stem cell transplantation and immunotherapy, and Cara Haymaker, cancer immunologist with expertise in immune biomarker analysis. They will be supported by a multidisciplinary team of world-class and highly collaborative experts on cancer and immunotherapy. The main goals of MDA-CIMAC are to: 1) provide a centralized and harmonized platform for sample collection, processing and quality assurance, and 2) use analytically-validated and standardized (Tiers 1 and 2) and highly innovative (Tier 3) assays to offer analyses for phenotypic, genomic, and functional characterization of responses of patients enrolled on IMT clinical trials. In Aim 1, we will utilize Standard Operating Procedures (SOPs) following the developed CIMAC umbrella protocol to provide services for processing and distribution of annotated biospecimens from the NCI-sponsored early phase immunotherapy clinical trials and to link the specimens to relevant clinical, pathological, immune and molecular data within the CIMAC-CIDC Network. In Aim 2, we will perform routine and innovative pathological, immunological and molecular analyses using standardized and validated and highly innovative assays to aid the completion of NCI- sponsored early phase clinical trials and the development of novel predictive IMT biomarkers. In Aim 3, in conjunction with the CIDC team, we will provide biostatistics and computational services for data collection and analysis, and will perform, interpret and predict modeling of high dimensional (‘omic”) data. We envision that the MDA-CIMAC will be indispensable as we make meaningful progress in cancer immunotherapeutic approaches.