High-Dimensional Immune Monitoring of NCI-Supported Immunotherapy Trials

NCI 支持的免疫治疗试验的高维免疫监测

• 批准号: 9457012
• 负责人: Sacha Gnjatic
• 金额: $ 1356万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9457012
• 关键词: Address; Aftercare; Antibodies; Antigens; Award; Bioinformatics; Biological; Biological Assay; Biological Markers; Biometry; Blood; CLIA certified; Cancer Patient; Clinical; Clinical Trials; Collection; Companions; Complement; Complex; Cytometry; Data; Data Analyses; Data Set; Development; Disease; Drug Evaluation; Enrollment; Enzyme-Linked Immunosorbent Assay; Funding; Future; Generations; Genomics; Goals; Immune; Immune response; Immunocompetence; Immunologic Markers; Immunologic Monitoring; Immunologist; Immunology procedure; Immunotherapy; Industry; Monitor; Outcome; PDCD1LG1 gene; Pathologist; Pathology; Patients; Peripheral; Pharmacodynamics; Phase; Phenotype; Population; Positioning Attribute; Protocols documentation; RNA; Sampling; Scheme; Serologic tests; Shotguns; Specialist; Specificity; Standardization; T cell response; Testing; Thinking; Tissues; Toxic effect; Tumor Antigens; Validation; Work; adaptive immune response; analytical tool; base; biomarker development; blood-based biomarker; cancer care; cancer immunotherapy; clinical biomarkers; clinical practice; data management; enzyme linked immunospot assay; high dimensionality; immune checkpoint blockade; innovation; member; metagenomic sequencing; microbiome; nano-string; novel therapeutics; oncology; predictive marker; protein biomarkers; response; single cell analysis; success; tool; transcriptome sequencing; trial design; tumor; vaccine trial

PROJECT SUMMARY Immunotherapy is transforming decades of clinical practice in cancer care, but it also comes with new questions about understanding mechanisms of action contributing to both antitumor activity and potential associated toxicity. Most importantly, identifying why only a fraction of patients derives clinical benefit is at the forefront of future developments, with the ever-elusive validation of useful clinical biomarkers as the ultimate goal. As a consortium of immunologists, technologists, clinicians, computational biologists, data specialists, and biostatisticians, the Mount Sinai CIMAC (MS-CIMAC) is uniquely positioned to generate immune profiling datasets at an unprecedented level of granularity to identify biomarker signatures of disease course and response to immunotherapy in cancer patients. MS-CIMAC will take full advantage of the smart cancer immunotherapy trial designs championed by the NCI that mandate collection of baseline and on-treatment biospecimens. Key strengths of MS-CIMAC are expected to be in unique high-dimensional yet sample-sparing approaches, including CyTOF mass cytometry, seromics, microbiome, and multiplex chromogen IHC, thanks to the implementation of cutting-edge yet validated protocols and analysis pipelines. Through a comprehensive array of assays and analytical tools that bridge innovation and standardization, MS-CIMAC intends to pursue the following three aims: a) help characterize immunocompetence at baseline and assess global immune changes during treatment, b) drill down the specificity and quality of immune responses for mechanistic evaluation of drugs, and c) automate, optimize, and integrate analyses of resulting datasets to facilitate sharing, and to ultimately discover composite immune biomarkers that will impact clinical cancer care.

项目摘要 免疫疗法正在改变数十年来癌症护理的临床实践，但它也带来了新的 关于理解有助于抗肿瘤活性和潜力的作用机制的问题 相关毒性。最重要的是，确定为什么只有一小部分患者获得临床获益是在 未来发展的最前沿，有用的临床生物标志物的验证是最终的 目标.作为免疫学家、技术专家、临床医生、计算生物学家、数据专家的联盟， 和生物统计学家，西奈山CIMAC（MS-CIMAC）是唯一的定位，以产生免疫分析 以前所未有的粒度水平收集数据集，以识别疾病过程的生物标志物特征， 对癌症患者免疫治疗的反应。MS-CIMAC将充分利用智能癌症 NCI倡导的免疫治疗试验设计，要求收集基线和治疗期间的 生物标本MS-CIMAC的主要优势预计将是独特的高维但样本节约 方法，包括CyTOF质谱细胞术，血清学，微生物组学和多重显色剂IHC，感谢 实施尖端但经过验证的协议和分析管道。通过全面 MS-CIMAC计划开发一系列连接创新和标准化的检测和分析工具， 以下三个目标：a）帮助表征基线免疫能力并评估总体免疫能力， B）深入研究免疫应答的特异性和质量， 药物评估，以及c）自动化，优化和整合结果数据集的分析，以促进 共享，并最终发现将影响临床癌症护理的复合免疫生物标志物。