Spatially Resolved, Multi-Omics Analyses of Immune Infiltrates in GBM Microenvironment

GBM 微环境中免疫浸润的空间分辨多组学分析

• 批准号: 10483889
• 负责人: Jennifer Mary Garbarino
• 金额: $ 25.11万
• 依托单位: ATLASXOMICS INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10483889
• 关键词: Antibodies; Automation; Bar Codes; Biological Assay; Brain; Brain Neoplasms; Capital; Cell Communication; Cells; Collaborations; Data; Development; Device Designs; Devices; Disease; Elements; Fishes; Flow Cytometry; Fluorescent in Situ Hybridization; Genes; Glioblastoma; Goals; Grant; Heterogeneity; Immune; Immune system; Immunofluorescence Immunologic; Immunophenotyping; Immunotherapy; Incidence; Injections; Malignant Neoplasms; Malignant neoplasm of brain; Maps; Measures; Membrane Proteins; Methods; Microfluidics; Microscopy; Mus; National Cancer Institute; Performance; Phase; Phenotype; Program Development; Proteins; Proteome; Proteomics; Research Personnel; Resolution; Sampling; Small Business Innovation Research Grant; Solid; Solid Neoplasm; Survival Rate; Technology; Tissues; Transcript; Tumor-infiltrating immune cells; Vaccines; Work; base; cancer immunotherapy; commercial application; design; detector; effective therapy; epigenome; genome-wide; improved; interest; mouse model; multiple omics; next generation; next generation sequencing; novel; novel therapeutics; patient prognosis; professor; protein biomarkers; single cell technology; single-cell RNA sequencing; specific biomarkers; success; technological innovation; therapy development; tool; transcriptome; transcriptomics; tumor microenvironment; tumor-immune system interactions; vaccine development

Abstract: In this SBIR grant, AtlasXomics Inc. proposes to develop a novel spatial immunophenotyping device that maps immune infiltrates in the mouse brain tumor microenvironment (TME) by spatially co-profiling ~20 immune surface protein biomarkers and the whole transcriptome (WT) with cellular resolution. In collaboration with researchers at the National Cancer Institute (NCI), we will demonstrate the ability of this device to richly characterize their potentially transformative immunotherapy for glioblastoma (GBM). Company founder Professor Rong Fan developed the basis for the device, Deterministic Barcoding in Tissue for spatial omics sequencing (DBiT-seq), to enable cellular-resolution mapping of the whole transcriptome, high- plex proteome, and genome-wide epigenome. AtlasXomics proposes in Phase I to develop a next-generation immunophenotyping device to map immune infiltrates in the TME by combining same-section WT and proteomic data. DBiT- seq’s unique microfluidics approach enables co-profiling of WT and proteins. The next-generation immunophenotyping device will build on the proven ability of protein biomarkers to characterize immune phenotypes by incorporating both cellular-resolution mapping and the discovery potential imparted by same-section WT coverage. Aim 1: Develop a spatial multi-omics immunophenotyping device (proteome and whole transcriptome) to identify and map immune infiltrates in the GBM microenvironment. Aim 2: Demonstrate application of the next generation immunophenotyping device by mapping and identifying immune infiltrates in NCI’s GBM mouse model. After Phase I, we will have demonstrated that the next generation immunophenotyping assay achieves cellular resolution co-profiling of whole transcriptome and a tailored protein panel, thereby enabling mapping and characterization of immune infiltrates in the TME. This device will help improve understanding of the mechanisms underlying various immunotherapy treatments. Upon demonstrating the value of the novel spatial immunophenotyping device to NCI’s vaccine development program, AtlasXomics will scale the product's throughput, robustness through semi-automation and advanced chip designs. An optimized mouse brain-specific multi-omics immunophenotyping device would enable cancer researchers to better understand how immune infiltration underpins cancer immunotherapy. A next generation immunophenotyping device combining cellular resolution proteomics and WT will become a standard tool to promote solid tumor cancer immunotherapy treatment development.

翻译后摘要：在这个SBIR补助金，Xomics公司。建议开发一个新的空间 免疫表型设备，其映射小鼠脑肿瘤中的免疫浸润 通过空间共分析~20种免疫表面蛋白生物标志物和微环境（TME）， 具有细胞分辨率的全转录组（WT）。在与国家研究人员的合作下， 癌症研究所（NCI），我们将证明这种设备的能力，以丰富的特点，他们的 胶质母细胞瘤（GBM）的潜在变革性免疫疗法。公司创始人教授 Rong Fan开发了该设备的基础，用于空间组学的组织中的确定性条形码 测序（DBiT-seq），以实现整个转录组的细胞分辨率映射， 复合蛋白质组和全基因组表观基因组。 Xomics在第一阶段提出开发下一代免疫表型设备， 通过结合相同切片WT和蛋白质组学数据绘制TME中的免疫浸润图。DBiT- seq独特的微流体方法可以实现WT和蛋白质的共同分析。下一代 免疫表型设备将建立在蛋白质生物标志物的证明能力，以表征 通过结合细胞分辨率映射和发现潜力， 相同的WT覆盖范围。 目的1：研制一种空间多组学免疫分型装置（蛋白质组和整体 转录组）以鉴定和绘制GBM微环境中的免疫浸润。 目标2：通过以下方式展示下一代免疫表型分析设备的应用： 在NCI的GBM小鼠模型中定位和鉴定免疫浸润。 在第一阶段之后，我们将证明下一代免疫表型分析 实现了整个转录组和定制蛋白质组的细胞分辨率共谱， 从而能够对TME中的免疫浸润进行定位和表征。这款设备将 有助于提高对各种免疫疗法治疗机制的理解。 在证明了新的空间免疫表型设备对NCI疫苗的价值后， 开发计划，Xomics将扩大产品的吞吐量，鲁棒性， 半自动化和先进的芯片设计。优化的小鼠脑特异性多组学 免疫表型分析设备将使癌症研究人员能够更好地了解免疫 浸润是癌症免疫治疗的基础。下一代免疫分型设备 将细胞分辨率蛋白质组学和WT相结合将成为促进固体蛋白质的标准工具。 肿瘤癌症免疫治疗的发展。