Living Tumor Biopsies to Interrogate Immune Function and Response to Therapy

活体肿瘤活检以询问免疫功能和对治疗的反应

• 批准号: 9135274
• 负责人: MATTHEW F KRUMMEL
• 金额: $ 19.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9135274
• 关键词: Antibody Therapy; Beds; Behavior; Biological Assay; Biopsy; Biopsy Specimen; Breast; Color; Combined Modality Therapy; Complex; Development; Diagnostic; Diagnostics Research; Dose; Formalin; Future; Glean; Health; Human; ITGAM gene; Image; Image Analysis; Immune; Immune response; Immune system; In Situ; Individual; Life; Lung; Malignant Neoplasms; Measures; Medicine; Methods; Mus; Myelogenous; Nature; Operative Surgical Procedures; Pathology; Patient Rights; Patients; Pattern; Pharmaceutical Preparations; Plant Roots; Population; Preparation; Process; Punch Biopsy; Reader; Reagent; Resistance; Route; Sampling; Selection for Treatments; Series; Skin; Slice; Staging; Staining method; Stains; Stream; T cell response; T-Lymphocyte; Technology; Testing; Therapeutic; Time; Tissues; Variant; Work; blind; cell motility; cohort; experience; field study; human disease; immune function; innovation; mouse model; novel; novel therapeutics; outcome forecast; predicting response; research study; responders and non-responders; response; sample fixation; spatiotemporal; therapeutic development; tumor; tumor microenvironment; two-photon

 DESCRIPTION (provided by applicant): Treating the immune response within tumors is a major focus of new therapeutic development. For emerging therapies, there are clear responders and non-responders and at present, we are blind to knowing in how many ways the immune system is deficient. We are also unable to know which of the current or emerging therapies will work for a given patient. The current best-approach is to put each patient through a sequence of therapies before (hopefully) hitting upon one that works. In the future, we believe we will be able to tap the wealth of information that is contained in the just-excised biopsy of each patient. Each biopsy contains significantly more information than we currently glean in the form of the spatiotemporal cellular interactions that are taking place therein. Many immune activities continue to occur when biopsies are collected, maintained and imaged under appropriate conditions. We hypothesize that it is possible to study the functionality of the human tumor microenvironment `live' by the development of standard practices for `live biopsy'. If we are right, patient samples can be both characterized overall but also used as a test-bed for single or combinations of therapies to determine the most likely one to induce tumor rejection. Rare, small and information-rich human biospecimens will be directly and reproducibly studied and will be critical in next-gen discovery and diagnostic platforms. This study will define a serie of parameters by which biopsy samples can enter this important discovery stream.

 描述（由申请人提供）：治疗肿瘤内的免疫反应是新治疗开发的主要焦点。对于新兴疗法，有明确的反应者和无反应者，目前，我们对免疫系统在多少方面存在缺陷一无所知。我们也无法知道目前或新兴的治疗方法将适用于特定的患者。目前最好的方法是让每个病人接受一系列治疗，然后（希望）找到一种有效的治疗方法。在未来，我们相信我们将能够挖掘每个患者刚刚切除的活检中所包含的丰富信息。每一个活组织切片所包含的信息都比我们目前收集的时空细胞相互作用的信息要多得多。在适当的条件下收集、保存和成像活检标本时，许多免疫活动继续发生。我们假设有可能通过发展“活组织检查”的标准实践来研究人类肿瘤微环境“活”的功能。如果我们是正确的，患者样本既可以整体表征，也可以用作单一或组合疗法的测试平台，以确定最有可能诱导肿瘤排斥的疗法。稀有、小型和信息丰富的人类生物标本将被直接和可重复地研究，并将在下一代发现和诊断平台中发挥关键作用。这项研究将定义一系列参数，通过这些参数，活检样本可以进入这一重要的发现流。