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Rapid highly multi-plexed immuno-profiling of solid tumors by SpectralEdge imaging

通过 SpectralEdge 成像对实体瘤进行快速高度多重免疫分析

基本信息

批准号：
10259793
负责人：
Eric Kaldjian
金额：
$ 84.78万
依托单位：
RARECYTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10259793
关键词：
Anatomy Antibodies Antigens Architecture Archives Autoimmunity Biological Assay Biotechnology Cancer Model Cell Communication Clinical Clinical Research Clinical Trials Communicable Diseases Computer software Data Data Collection Development Diagnostic Diagnostic Procedure Diagnostic tests Documentation Engineering Environment Fluorescence Formalin Future Genetic Engineering Grant Hour Human Image Image Analysis Imaging technology Immune Immune checkpoint inhibitor Immune system Immunofluorescence Immunologic Immunooncology Immunophenotyping Immunotherapy Individual Industry Label Laboratories Legal patent Location Malignant Neoplasms Malignant neoplasm of lung Maps Measures Mechanics Methods Microscope Molecular Profiling Mus Nurses&apos Health Study Oncologist Optics Paraffin Embedding Pathologist Pathology Patient Care Patients Periodicity Pharmaceutical Preparations Pharmacodynamics Phase Phase II Clinical Trials Production Prognostic Marker Proteins Reagent Research Research Personnel Resistance Resolution Sampling Sampling Studies Scanning Scientist Signal Transduction Slide Solid Neoplasm Specimen Stromal Cells System Technology Testing Therapeutic Time Tissue imaging Tissues Translational Research Tumor-infiltrating immune cells Validation antibody conjugate base biomarker discovery cancer diagnosis cancer type cell type cellular imaging checkpoint inhibition clinically actionable cohort data format data standards design digital pathology drug development fluorescence imaging fluorophore image processing imager imaging capabilities imaging modality imaging system immune activation improved instrument instrumentation interest malignant breast neoplasm medical schools meetings mouse model neoplastic cell novel novel therapeutics oncology trial patient response pembrolizumab performance tests predictive marker preservation programs response tool tumor tumor microenvironment whole slide imaging

项目摘要

PROJECT SUMMARY – ABSTRACT The dramatic impact of immune checkpoint inhibitors (ICIs) has focused interest in investigating immune-tumor cell interactions to understand mechanisms of ICI sensitivity and resistance, to identify patients responsive to specific drugs, and to develop new therapies. Multiplexed tissue imaging is a highly promising approach to tumor immunoprofiling: it can assess many cell types and states within the context of preserved tumor architecture and is compatible with pathology workflows. A critical unmet need exists for multiplex technology with the following capabilities: (1) whole-slide imaging; (2) rapid single-pass data collection; (3) sub- cellular imaging resolution; (4) sufficient immunoprofiling depth; (5) bright-field imaging capability; (6) optical and mechanical stability for accurate image tile stitching; (7) availability of core and customizable antibody panel kits for profiling; and (8) compatibility with established image data standards and formats. This RareCyte – Harvard Medical School Phase II proposal describes SpectralEdgeTM, a breakthrough imaging technology that meets these requirements, performing high-resolution high-plex whole-slide imaging of 20 antigens labelled with fluorophore-conjugated antibodies in a single-pass scan of less than 1 hour. The patented SpectralEdge method involves a novel instrument and software as well as highly validated TissuePlexTM antibody panels. SpectralEdge imaging will accelerate discovery of predictive and prognostic biomarkers, enable pharmacodynamics study of immuno-oncology drugs undergoing clinical trials and ultimately provide clinically actionable diagnostic tests. Aim 1 will focus on engineering and production of a robust, production-ready slide scanner and software for rapid high-resolution 20-plex SpectralEdge whole-slide imaging; it will be based on RareCyte’s existing CyteFinder II imaging system. Production of a research-use-only instrument and reagents to ISO13485 standards will enable subsequent deployment in a clinical setting. Compatibility with current and emerging data format and software standards will enable integration with diverse research and clinical workstreams. Aim 2 will test and validate modular antibody panels for immunophenotyping and tumor cell imaging across a range of tumor types. This will yield validated TissuePlex panels having a core set of immunoprofiling antibodies and antibody “modules” for individual tumor types. Aim 3 will test SpectralEdge imaging on well-characterized sample cohorts in: (i) translational biomarker discovery, (ii) industry-sponsored and investigator-initiated immuno-oncology trials, (iii) mouse models of cancer, and (iv) clinical specimens currently undergoing immunoprofiling with other diagnostic methods. Clinical sample studies will be overseen by an advisory group of board-certified HMS pathologists.

项目摘要-摘要免疫检查点抑制剂(ICIS)的巨大影响引起了人们的研究兴趣免疫-肿瘤细胞相互作用以了解ICI敏感性和耐药性的机制，以识别患者对特定药物的反应，并开发新的治疗方法。多路组织成像是一种非常有前途的技术肿瘤免疫分析的方法：它可以在保存的背景下评估许多细胞类型和状态肿瘤架构，并与病理工作流程兼容。对多厅影院的迫切需求尚未得到满足具有以下能力的技术：(1)全幻灯片成像；(2)快速单程数据收集；(3)亚细胞成像分辨率；(4)足够的免疫图谱深度；(5)明场成像能力；(6)光学和机械稳定性，以实现准确的图像拼接；(7)核心和可定制抗体的可用性用于分析的面板套件；以及(8)与已建立的图像数据标准和格式的兼容性。这份RareCyte-哈佛医学院第二阶段提案描述了SpectralEdgeTM的一项突破符合这些要求的成像技术，执行高分辨率高复数全幻灯片成像在不到1小时的单次扫描中，用荧光团标记的抗体标记了20个抗原。这个专利的SpectralEdge方法涉及一种新的仪器和软件，以及高度验证的 TIsePlexTM抗体板。光谱边缘成像将加速发现预测性和预见性生物标志物，使正在进行临床试验的免疫肿瘤药物的药效学研究成为可能最终提供临床上可行的诊断测试。目标1将专注于设计和生产一种坚固耐用、可用于生产的幻灯片扫描仪和用于快速高分辨率20倍光谱边缘全幻灯片成像的软件；它将基于RareCyte的现有的CyteFinder II成像系统。仅供研究使用的仪器和试剂的生产 ISO13485标准将使随后在临床环境中部署成为可能。与当前和新兴的数据格式和软件标准将使不同的研究和临床集成成为可能工作流。 AIM 2将测试和验证用于免疫表型和肿瘤细胞成像的模块化抗体面板在一系列肿瘤类型中。这将产生经过验证的TIsePlex面板，该面板具有一套核心的免疫简档针对个别肿瘤类型的抗体和抗体“模块”。 AIM 3将在特征良好的样本队列上测试SpectralEdge成像：(I)翻译生物标记物发现，(Ii)工业赞助和研究人员发起的免疫肿瘤学试验，(Iii)小鼠癌症模型，以及(Iv)目前正在接受免疫分析的临床标本方法：研究方法。临床样本研究将由一个由委员会认证的HMS病理学家组成的咨询小组监督。