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

摘要：在这笔SBIR赠款中，AtlasXonomy Inc.提议开发一种新的空间 绘制小鼠脑瘤免疫浸润区的免疫表型分析装置 微环境(TME)通过空间共剖析~20个免疫表面蛋白生物标志物和 具有细胞分辨率的完整转录组(WT)。与国家科学研究院的研究人员合作 癌症研究所(NCI)，我们将演示该设备的能力，以丰富地表征他们的 胶质母细胞瘤(GBM)的潜在变革性免疫疗法。公司创始人教授 荣凡开发了该设备的基础，即用于空间组学的组织内确定性条形码 测序(DBiT-seq)，以实现整个转录组的细胞分辨率图谱，高- Plex蛋白质组和全基因组表观基因组。 AtlasXology在第一阶段建议开发下一代免疫表型设备，以 结合同一切片的WT和蛋白质组数据，绘制免疫在TME中的浸润图。DBiT- SEQ独特的微流控方法使WT和蛋白质的联合图谱成为可能。下一代 免疫表型设备将建立在已证实的蛋白质生物标记物表征能力的基础上 结合细胞分辨图谱和发现潜力的免疫表型 由同一节WT报道传授。 目的1：研制空间多组学免疫表型测定仪(蛋白质组和整体 转录组)，以识别和定位GBM微环境中的免疫渗透。 目标2：通过以下方式展示下一代免疫表型设备的应用 定位和识别NCI的GBM小鼠模型中的免疫渗透。 在第一阶段之后，我们将展示下一代免疫表型分析 实现了对整个转录组和定制蛋白质组的细胞分辨率共同分析， 从而能够对TME中的免疫浸润物进行映射和表征。这台设备将 有助于提高对各种免疫疗法治疗机制的理解。 展示新型空间免疫分型装置对NCI疫苗的价值 开发计划，AtlasXonics将通过以下方式扩展产品的吞吐量和健壮性 半自动和先进的芯片设计。一种优化的小鼠脑特异性多组学研究 免疫表型设备将使癌症研究人员能够更好地了解免疫 浸润性是癌症免疫治疗的基础。新一代免疫表型测定仪 结合细胞分辨蛋白质组学和WT将成为促进固体 肿瘤免疫治疗进展。

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.