I-Corps: Immune Profiling for Patient Stratification in Clinical Drug Development of Autoimmune and Cancer Biologic Therapies

这个i-Corps项目的更广泛的影响/商业潜力正在验证使用全面的免疫图谱技术来识别预测生物标记物的价值，以简化临床试验药物开发。如果与反应灵敏的患者群体相匹配，靶向治疗可能非常有效。在临床开发中，提高治疗效果、降低成本和降低治疗风险的一种方法是将患者群体细分为可能的应答者和无应答者。这种免疫图谱技术有可能通过识别与治疗相关的预测性生物标志物，以这种方式对患者进行分层。该项目的重点是自身免疫性疾病的免疫疗法和生物制品，这两个领域的免疫系统活动是治疗成功和避免不良副作用的核心。通过检查患者的免疫状况，该项目希望确定错误调节的细胞和基因途径，从而阐明患者的治疗效果。预测患者对治疗的反应将简化临床试验药物审批，降低无效治疗的医疗成本，并最终改善患者结果。这个i-Corps项目基于一个强大的基于测序的免疫图谱平台，用于精确医学和药物开发应用中的患者分层。这项技术使高通量分离和直接从微升全血中提取单个免疫细胞的全面转录图谱成为可能。根据产生的数据，开发了高分辨率、多尺度的免疫图谱，呈现了不同细胞类型和单个细胞内的相互作用的读数。这些无偏见的高维图谱提供了三个不同的信息层：1)细胞水平：观察到的每种细胞类型的频率，2)模块水平：炎症和免疫途径的转录程序，以及3)基因水平：每种细胞类型中的单个生物标志物。与DNA测序相比，这些测量对细胞异质性敏感，并捕获了驱动疾病发病机制和药物治疗反应的动态过程的遗传和环境因素。免疫状态的这种紧凑表示将使识别免疫简档的特征成为可能，这些特征预测疾病、药物反应等。

The broader impact/commercial potential of this I-Corps project is validating the value of using a comprehensive immune profiling technology to identify predictive biomarkers for streamlining clinical trial drug development. Targeted treatments can be very effective when matched with a responsive patient population. One way to increase treatment efficacy, reduce cost, and mitigate risk for therapies in clinical development is to sub-segment a patient population into likely responders and non-responders. This immune profiling technology has the potential to stratify patients this way by identifying predictive biomarkers that correlate with treatment. The project's focus is on immunotherapies and biologics for autoimmune diseases, two areas where the immune system activity is central to therapy success and avoidance of adverse side effects. By examining the immune profile of patients, this project hopes to identify mis-regulated cellular and gene pathways and therefore elucidate therapeutic efficacy in patients. Predicting patient response to therapies will streamline clinical trial drug approval, reduce healthcare costs on ineffective treatments, and ultimately, improve patient outcomes.This I-Corps project is based on a powerful sequencing-based immune profiling platform for patient stratification for applications in precision medicine and drug development. This technology enables high-throughput isolation and comprehensive transcriptional profiling of individual immune cells directly from microliters of whole blood. From the data generated, high-resolution, multi-scale immune profiles are developed that present a readout of the interactions across cell types and within individual cells. These unbiased and high-dimensional profiles provide three distinct tiers of information: 1) Cellular level: the frequency of each cell type observed, 2) Module level: the transcriptional programs for inflammatory and immune pathways and 3) Gene level: individual biomarkers within each cell type. In contrast to DNA sequencing, these measurements are sensitive to cellular heterogeneity and captures the genetic and environmental factors driving the dynamic processes of disease pathogenesis and response to drug therapy. This compact representation of the immune state will enable the identifcation of features of the immune profile that are predictive of disease, drug response, and more.